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cytomegaloviral determinants of cd8+ t cell programming and rhcmv/siv vaccine efficacy.simian immunodeficiency virus (siv) insert-expressing, 68-1 rhesus cytomegalovirus (rhcmv/siv) vectors elicit major histocompatibility complex e (mhc-e)- and mhc-ii-restricted, siv-specific cd8+ t cell responses, but the basis of these unconventional responses and their contribution to demonstrated vaccine efficacy against siv challenge in the rhesus monkeys (rms) have not been characterized. we show that these unconventional responses resulted from a chance genetic rearrangement in 68-1 rhcmv t ...202133766849
interleukin-15 response signature predicts rhcmv/siv vaccine efficacy.simian immunodeficiency virus (siv) challenge of rhesus macaques (rms) vaccinated with strain 68-1 rhesus cytomegalovirus (rhcmv) vectors expressing siv proteins (rhcmv/siv) results in a binary outcome: stringent control and subsequent clearance of highly pathogenic siv in ~55% of vaccinated rms with no protection in the remaining 45%. although previous work indicates that unconventionally restricted, siv-specific, effector-memory (em)-biased cd8+ t cell responses are necessary for efficacy, the ...202134228762
animal models of congenital cytomegalovirus transmission: implications for vaccine development.although cytomegaloviruses (cmvs) are species-specific, the study of nonhuman cmvs in animal models can help to inform and direct research aimed at developing a human cmv (hcmv) vaccine. because the driving force behind the development of hcmv vaccines is to prevent congenital infection, the animal model in question must be one in which vertical transmission of virus occurs to the fetus. fortunately, two such animal models-the rhesus macaque cmv and guinea pig cmv-are characterized by congenital ...202032134481
rhesus cytomegalovirus-specific cd8+ cytotoxic t lymphocytes do not become functionally exhausted in chronic sivmac239 infection.cd8+ cytotoxic t lymphocytes (ctls) exert potent antiviral activity after hiv/siv infection. however, efforts to harness the antiviral efficacy of ctls for hiv/siv prophylaxis and therapy have been severely hindered by two major problems: viral escape and exhaustion. by contrast, ctls directed against human cytomegalovirus (hcmv), a ubiquitous chronic herpesvirus, seldom select for escape mutations and remain functional and refractory to exhaustion during chronic hcmv and hiv infection. recently ...202032922404
rhcmv serostatus and vaccine adjuvant impact immunogenicity of rhcmv/siv vaccines.rhesus cytomegalovirus (rhcmv) strain 68-1-vectored simian immunodeficiency virus (rhcmv/siv) vaccines are associated with complete clearance of pathogenic siv challenge virus, non-canonical major histocompatibility complex restriction, and absent antibody responses in recipients previously infected with wild-type rhcmv. this report presents the first investigation of rhcmv/siv vaccines in rhcmv-seronegative macaques lacking anti-vector immunity. fifty percent of rhesus macaques (rm) vaccinated ...202032820216
immunophenotyping of rhesus cmv-specific cd8 t-cell populations.a vaccine to ameliorate cytomegalovirus (cmv)-related pathogenicity in transplantation patients is considered a top priority. a therapeutic vaccine must include components that elicit both neutralizing antibodies, and highly effective cd8 t-cell responses. the most important translational model of vaccine development is the captive-bred rhesus macaque (macaca mulatta) of indian origin. there is a dearth of information on rhesus cytomegalovirus (rhcmv)-specific cd8 t cells due to the absence of w ...202032713108
in vitro and in vivo characterization of a recombinant rhesus cytomegalovirus containing a complete genome.cytomegaloviruses (cmvs) are highly adapted to their host species resulting in strict species specificity. hence, in vivo examination of all aspects of cmv biology employs animal models using host-specific cmvs. infection of rhesus macaques (rm) with rhesus cmv (rhcmv) has been established as a representative model for infection of humans with hcmv due to the close evolutionary relationships of both host and virus. however, the only available rhcmv clone that permits genetic modifications is bas ...202033232376
a live-attenuated rhcmv/siv vaccine shows long-term efficacy against heterologous siv challenge.previous studies have established that strain 68-1-derived rhesus cytomegalovirus (rhcmv) vectors expressing simian immunodeficiency virus (siv) proteins (rhcmv/siv) are able to elicit and maintain cellular immune responses that provide protection against mucosal challenge of highly pathogenic siv in rhesus monkeys (rms). however, these efficacious rhcmv/siv vectors were replication and spread competent and therefore have the potential to cause disease in immunocompromised subjects. to develop a ...201931316007
enhancing safety of cytomegalovirus-based vaccine vectors by engaging host intrinsic immunity.rhesus cytomegalovirus (rhcmv)-based vaccines maintain effector memory t cell responses (tem) that protect ~50% of rhesus monkeys (rms) challenged with simian immunodeficiency virus (siv). because human cmv (hcmv) causes disease in immunodeficient subjects, clinical translation will depend upon attenuation strategies that reduce pathogenic potential without sacrificing cmv's unique immunological properties. we demonstrate that "intrinsic" immunity can be used to attenuate strain 68-1 rhcmv vecto ...201931316006
neutralization of rhesus cytomegalovirus il-10 reduces horizontal transmission and alters long-term immunity.human cytomegalovirus (hcmv) causes severe disease in infants and immunocompromised people. there is no approved hcmv vaccine, and vaccine development strategies are complicated by evidence of both persistent infection and reinfection of people with prior immunity. the greatest emphasis has been placed on reducing transmission to seronegative pregnant women to prevent vertical transmission and its potentially severe sequelae. increasing evidence suggests that the earliest host-hcmv interactions ...201931189602
comparison of vaccination with rhesus cmv (rhcmv) soluble gb with a rhcmv replication-defective virus deleted for mhc class i immune evasion genes in a rhcmv challenge model.a human cytomegalovirus (hcmv) vaccine to prevent infection and/or reduce disease associated with congenital infection or visceral disease in transplant recipients is a high priority, but has remained elusive. we created a disabled infectious single cycle rhesus cmv (rhcmv) deleted for glycoprotein l (gl) and the mhc class i immune evasion genes rh178 and rh182-189, and restored its epithelial cell tropism by inserting the rh128-131a genes. the resulting virus, rhcmvrδgl/178/182-189, was used to ...201930522906
identification and functional characterization of a novel fc gamma-binding glycoprotein in rhesus cytomegalovirus.receptors recognizing the fc part of immunoglobulin g (fcγrs) are key determinants in antibody-mediated immune responses. members of the herpesviridae interfere with this immune regulatory network by expressing viral fcγrs (vfcγrs). human cytomegalovirus (hcmv) encodes four distinct vfcγrs that differ with respect to their igg subtype specificity and their impact on antibody-mediated immune function in vitro the impact of vfcγrs on hcmv pathogenesis and immunomodulation in vivo is not known. the ...201930487278
vaccine-mediated inhibition of the transporter associated with antigen processing is insufficient to induce major histocompatibility complex e-restricted cd8+ t cells in nonhuman primates.major histocompatibility complex e (mhc-e) is a highly conserved nonclassical mhc-ib molecule that tightly binds peptides derived from leader sequences of classical mhc-ia molecules for presentation to natural killer cells. however, mhc-e also binds diverse foreign and neoplastic self-peptide antigens for presentation to cd8+ t cells. although the determinants of mhc-e-restricted t cell priming remain unknown, these cells are induced in humans infected with pathogens containing genes that inhibi ...201931315990
long-term safety outcome of systemic immunosuppression in pig-to-nonhuman primate corneal xenotransplantation.safety concerns exist for corneal recipients under immunosuppression. we report long-term safety results of porcine corneal xenotransplantation under immunosuppression in nonhuman primates.201830264877
cmv primes functional alternative signaling in adaptive δg nk cells but is subverted by lentivirus infection in rhesus macaques.despite burgeoning evidence demonstrating the adaptive properties of natural killer (nk) cells, mechanistic data explaining these phenomena are lacking. following antibody sensitization, nk cells lacking the fc receptor (fcr) signaling chain (δg) acquire adaptive features, including robust proliferation, multifunctionality, rapid killing, and mobilization to sites of virus exposure. using the rhesus macaque model, we demonstrate the systemic distribution of δg nk cells expressing memory features ...201830517864
prevention of tuberculosis in rhesus macaques by a cytomegalovirus-based vaccine.despite widespread use of the bacille calmette-guérin (bcg) vaccine, tuberculosis (tb) remains a leading cause of global mortality from a single infectious agent (mycobacterium tuberculosis or mtb). here, over two independent mtb challenge studies, we demonstrate that subcutaneous vaccination of rhesus macaques (rms) with rhesus cytomegalovirus vectors encoding mtb antigen inserts (hereafter referred to as rhcmv/tb)-which elicit and maintain highly effector-differentiated, circulating and tissue ...201829334373
natural history of postnatal rhesus cytomegalovirus shedding by dams and acquisition by infant rhesus monkeys.human infants frequently acquire human cytomegalovirus (hcmv) through breastfeeding, resulting in persistent high-level viral shedding in saliva and urine and infectivity to others, including pregnant women. thus, vaccination to interrupt postnatal hcmv transmission is an attractive strategy to prevent hcmv spread and congenital infection. rhesus cmv (rhcmv) in nonhuman primates is a valuable model for the study of immune strategies to prevent cmv transmission. although rhesus monkeys typically ...201830356332
early antiretroviral therapy limits siv reservoir establishment to delay or prevent post-treatment viral rebound.prophylactic vaccination of rhesus macaques with rhesus cytomegalovirus (rhcmv) vectors expressing simian immunodeficiency virus (siv) antigens (rhcmv/siv) elicits immune responses that stringently control highly pathogenic siv infection, with subsequent apparent clearance of the infection, in ~50% of vaccinees. in contrast, here, we show that therapeutic rhcmv/siv vaccination of rhesus macaques previously infected with siv and given continuous combination antiretroviral therapy (cart) beginning ...201830082858
cytomegaloviral hypophysitis in a simian immunodeficiency virus-infected rhesus macaque (macacca mulatta).rhesus macaques experimentally infected with simian immunodeficiency virus (siv) experience immunosuppression and often opportunistic infection. among the most common opportunistic infections are rhesus cytomegalovirus (rhcmv), a ubiquitous betaherpesvirus that undergoes continuous low-level replication in immunocompetent monkeys. upon siv-mediated immunodeficiency, rhcmv reactivates and results in lesions in numerous organ systems including the nervous and reproductive systems. we report the fi ...201728671330
unusual antigen presentation offers new insight into hiv vaccine design.recent findings with a rhesus monkey cytomegalovirus based simian immunodeficiency virus vaccine have identified strong cd8+ t cell responses that are restricted by mhc-e. also mycobacteria specific cd8+ t cells, that are mhc-e restricted, have been identified. mhc-e therefore can present a wide range of epitope peptides to cd8+ t cells, alongside its well defined role in presenting a conserved mhc-class i signal peptide to the nkg2a/c-cd94 receptor on natural killer cells. here we explore the a ...201728505602
inhibitors of dual-specificity tyrosine phosphorylation-regulated kinases (dyrk) exert a strong anti-herpesviral activity.infection with human cytomegalovirus (hcmv) is a serious medical problem, particularly in immunocompromised individuals and neonates. the success of (val)ganciclovir therapy is hampered by low drug compatibility and induction of viral resistance. a novel strategy of antiviral treatment is based on the exploitation of cell-directed signaling, e. g. pathways with a known relevance for carcinogenesis and tumor drug development. here we describe a principle for putative antiviral drugs based on targ ...201728400201
antagonism of the protein kinase r pathway in human cells by rhesus cytomegalovirus.while cytomegalovirus (cmv) infections are often limited in host range by lengthy coevolution with a singular host species, a few cmvs are known to deviate from this rule. for example, rhesus macaque cmv (rhcmv), a model for human cmv (hcmv) pathogenesis and vaccine development, can replicate in human cells, as well as in rhesus cells. both hcmv and rhcmv encode species-specific antagonists of the broadly acting host cell restriction factor protein kinase r (pkr). although the rhcmv antagonist o ...201729263260
plasmablast response to primary rhesus cytomegalovirus infection in a monkey model of congenital cmv transmission.human cytomegalovirus (hcmv) is the most common congenital infection worldwide, and the leading infectious cause of neurologic deficits and hearing loss in newborns. development of a maternal hcmv vaccine to prevent vertical virus transmission is a high priority, yet protective maternal immune responses following acute infection are poorly understood. to characterize the maternal humoral immune response to primary cmv infection, we investigated the plasmablast and early antibody repertoire using ...201728298291
broadly targeted cd8⁺ t cell responses restricted by major histocompatibility complex e.major histocompatibility complex e (mhc-e) is a highly conserved, ubiquitously expressed, nonclassical mhc class ib molecule with limited polymorphism that is primarily involved in the regulation of natural killer (nk) cells. we found that vaccinating rhesus macaques with rhesus cytomegalovirus vectors in which genes rh157.5 and rh157.4 are deleted results in mhc-e-restricted presentation of highly varied peptide epitopes to cd8αβ(+) t cells, at ~4 distinct epitopes per 100 amino acids in all te ...201626797147
natural killer cell evasion is essential for infection by rhesus cytomegalovirus.the natural killer cell receptor nkg2d activates nk cells by engaging one of several ligands (nkg2dls) belonging to either the mic or ulbp families. human cytomegalovirus (hcmv) ul16 and ul142 counteract this activation by retaining nkg2dls and us18 and us20 act via lysomal degradation but the importance of nk cell evasion for infection is unknown. since nkg2dls are highly conserved in rhesus macaques, we characterized how nkg2dl interception by rhesus cytomegalovirus (rhcmv) impacts infection i ...201627580123
exploitation of interleukin-10 (il-10) signaling pathways: alternate roles of viral and cellular il-10 in rhesus cytomegalovirus infection.there is accumulating evidence that the viral interleukin-10 (vil-10) ortholog of both human and rhesus cytomegalovirus (hcmv and rhcmv, respectively) suppresses the functionality of cell types that are critical to contain virus dissemination and help shape long-term immunity during the earliest virus-host interactions. in particular, exposure of macrophages, peripheral blood mononuclear cells, monocyte-derived dendritic cells, and plasmacytoid dendritic cells to vil-10 suppresses multiple effec ...201627558431
the susceptibility of primary cultured rhesus macaque kidney epithelial cells to rhesus cytomegalovirus strains.kidney epithelial cells are common targets for human and rhesus cytomegalovirus (hcmv and rhcmv) in vivo, and represent an important reservoir for long-term cmv shedding in urine. to better understand the role of kidney epithelial cells in primate cmv natural history, primary cultures of rhesus macaque kidney epithelial cells (mke) were established and tested for infectivity by five rhcmv strains, including two wild-type strains (ucd52 and ucd59) and three strains containing different coding con ...201626974598
cross-species rhesus cytomegalovirus infection of cynomolgus macaques.cytomegaloviruses (cmv) are highly species-specific due to millennia of co-evolution and adaptation to their host, with no successful experimental cross-species infection in primates reported to date. accordingly, full genome phylogenetic analysis of multiple new cmv field isolates derived from two closely related nonhuman primate species, indian-origin rhesus macaques (rm) and mauritian-origin cynomolgus macaques (mcm), revealed distinct and tight lineage clustering according to the species of ...201627829026
examining the species-specificity of rhesus macaque cytomegalovirus (rhcmv) in cynomolgus macaques.cytomegalovirus (cmv) is a highly species-specific virus that has co-evolved with its host over millions of years and thus restricting cross-species infection. to examine the extent to which host restriction may prevent cross-species research between closely related non-human primates, we evaluated experimental infection of cynomolgus macaques with a recombinant rhesus macaque-derived cmv (rhcmv-egfp). twelve cynomolgus macaques were randomly allocated to three groups: one experimental group (rh ...201525822981
correction: examining the species-specificity of rhesus macaque cytomegalovirus (rhcmv) in cynomolgus macaques. 201525973867
experimental evolution identifies vaccinia virus mutations in a24r and a35r that antagonize the protein kinase r pathway and accompany collapse of an extragenic gene amplification.most new human infectious diseases emerge from cross-species pathogen transmissions; however, it is not clear how viruses adapt to productively infect new hosts. host restriction factors represent one species-specific barrier that viruses may initially have little ability to inhibit in new hosts. for example, viral antagonists of protein kinase r (pkr) vary in their ability to block pkr-mediated inhibition of viral replication, in part due to pkr allelic variation between species. we previously ...201526202237
optimization of a novel non-invasive oral sampling technique for zoonotic pathogen surveillance in nonhuman primates.free-ranging nonhuman primates are frequent sources of zoonotic pathogens due to their physiologic similarity and in many tropical regions, close contact with humans. many high-risk disease transmission interfaces have not been monitored for zoonotic pathogens due to difficulties inherent to invasive sampling of free-ranging wildlife. non-invasive surveillance of nonhuman primates for pathogens with high potential for spillover into humans is therefore critical for understanding disease ecology ...201526046911
rhesus cytomegalovirus (macacine herpesvirus 3)-associated facial neuritis in simian immunodeficiency virus-infected rhesus macaques (macaca mulatta).peripheral neuropathies are common sequelae to human immunodeficiency virus (hiv) infection in humans and are due to a variety of mechanisms, including direct antiretroviral toxicity, hiv-mediated damage, immune-mediated disorders, and opportunistic viral infections. rhesus macaques (macaca mulatta) infected with simian immunodeficiency virus (siv) remain the most consistent animal model for unraveling the pathogenesis of lentiviral-associated disease and its associated opportunistic infections. ...201524686387
transcription of true late (γ2) cytomegalovirus genes requires ul92 function that is conserved among beta- and gammaherpesviruses.human cytomegalovirus-encoded ul92 plays an essential role in viral replication that has not been resolved. we show here that this gene controls the accumulation of true late (γ2) viral transcripts, a property shared with several other recently evaluated genes (ul79, ul87, ul91, and ul95) conserved among beta- and gammaherpesviruses. when the ul92 mutant virus was evaluated, function was fully complemented by either the natural protein or the homologous rh127 protein from rhesus cytomegalovirus. ...201424131715
atypical nodular astrocytosis in simian immunodeficiency virus-infected rhesus macaques (macaca mulatta).simian immunodeficiency virus (siv), a model for hiv pathogenesis, is associated with neuropathology.201425082291
a seroprevalence study of primate workers for asymptomatic rhesus cytomegalovirus infection.human cytomegalovirus (hcmv) infection can cause severe disease in neonates and immunocompromised persons, and infectious mononucleosis in healthy adults. while, rhesus cmv (rhcmv) infects human cells in culture, it is unknown whether the virus can infect humans.201424890818
limited dissemination and shedding of the ul128 complex-intact, ul/b'-defective rhesus cytomegalovirus strain 180.92.the ul128 complex of human cytomegalovirus (cmv) is a major determinant of viral entry into epithelial and endothelial cells and a target for vaccine development. the ul/b' region of rhesus cmv contains several open reading frames, including orthologs of the ul128 complex. we recently showed that the coding content of the rhesus cmv (rhcmv) ul/b' region predicts acute endothelial tropism and long-term shedding in vivo in the rhesus macaque model of cmv infection. the laboratory-passaged rhcmv 18 ...201424899204
postnatal acquisition of primary rhesus cytomegalovirus infection is associated with prolonged virus shedding and impaired cd4+ t lymphocyte function.although virus-specific cd4(+) t lymphocytes emerge rapidly during primary cytomegalovirus (cmv) infection in humans, they exhibit a state of prolonged functional exhaustion of unknown etiology. to investigate the suitability of rhesus macaques as a model of primary human cmv infection, we examined the virologic and immunologic features of naturally acquired primary cmv infection in rhesus macaques.201424719473
adaptive gene amplification as an intermediate step in the expansion of virus host range.the majority of recently emerging infectious diseases in humans is due to cross-species pathogen transmissions from animals. to establish a productive infection in new host species, viruses must overcome barriers to replication mediated by diverse and rapidly evolving host restriction factors such as protein kinase r (pkr). many viral antagonists of these restriction factors are species specific. for example, the rhesus cytomegalovirus pkr antagonist, rhtrs1, inhibits pkr in some african green m ...201424626510
mesenchymoproliferative enteropathy associated with dual simian polyomavirus and rhesus cytomegalovirus infection in a simian immunodeficiency virus-infected rhesus macaque (macaca mulatta).opportunistic viral infections are common in simian immunodeficiency virus-infected rhesus macaques and include simian polyomavirus 40 (sv40), which causes interstitial nephritis, pneumonia, meningoencephalitis, and progressive multifocal leukoencephalopathy and rhesus cytomegalovirus (macacine herpesvirus-3), which is associated with many pathologic manifestations, including the formation of neutrophil-rich gastrointestinal masses. herein we report the findings of a simian immunodeficiency viru ...201323051916
vaccination against a virus-encoded cytokine significantly restricts viral challenge.identification of immune correlates of protection for viral vaccines is complicated by multiple factors, but there is general consensus on the importance of antibodies that neutralize viral attachment to susceptible cells. development of new viral vaccines has mostly followed this neutralizing antibody paradigm, but as a recent clinical trial of human cytomegalovirus (hcmv) vaccination demonstrated, this singular approach can yield limited protective efficacy. since hcmv devotes >50% of its codi ...201323946461
immune clearance of highly pathogenic siv infection.established infections with the human and simian immunodeficiency viruses (hiv and siv, respectively) are thought to be permanent with even the most effective immune responses and antiretroviral therapies only able to control, but not clear, these infections. whether the residual virus that maintains these infections is vulnerable to clearance is a question of central importance to the future management of millions of hiv-infected individuals. we recently reported that approximately 50% of rhesu ...201324025770
cytomegalovirus vectors violate cd8+ t cell epitope recognition paradigms.cd8(+) t cell responses focus on a small fraction of pathogen- or vaccine-encoded peptides, and for some pathogens, these restricted recognition hierarchies limit the effectiveness of antipathogen immunity. we found that simian immunodeficiency virus (siv) protein-expressing rhesus cytomegalovirus (rhcmv) vectors elicit siv-specific cd8(+) t cells that recognize unusual, diverse, and highly promiscuous epitopes, including dominant responses to epitopes restricted by class ii major histocompatibi ...201323704576
a vaccine based on the rhesus cytomegalovirus ul128 complex induces broadly neutralizing antibodies in rhesus macaques.neutralizing antibodies (nab) are important for interfering with horizontal transmission of human cytomegalovirus (hcmv) leading to primary and congenital hcmv infection. recent findings have shown that a pentameric virion complex formed by the glycoproteins gh/gl, ul128, ul130, and ul131a (ul128c) is required for hcmv entry into epithelial/endothelial cells (epi/ec) and is the target of potent nab in hcmv-seropositive individuals. using bacterial artificial chromosome technology, we have genera ...201323152525
coding potential of ul/b' from the initial source of rhesus cytomegalovirus strain 68-1.rhesus cytomegalovirus (rhcmv) 68-1 is the prototypic strain of rhcmv that has been used for pathogenesis and vaccine development. we determined the complete sequence of the rhcmv 68-1 ul/b' region directly from the original urine from which rhcmv 68-1 was isolated in 1968, and compared it to other rhcmvs. the laboratory passaged rhcmv 68-1 has inversions, deletions, and stop codons in ul/b' that are absent in the original isolate and other low passage rhcmv isolates. fourteen of the 17 open rea ...201324210116
rhesus cytomegalovirus encodes seventeen micrornas that are differentially expressed in vitro and in vivo.human cytomegalovirus (hcmv) mirnas are important for regulation of viral infection and evasion of host immune responses. unfortunately, the importance of hcmv mirnas cannot be addressed in vivo due to the species specificity of cmvs. rhesus cmv (rhcmv) infection of rhesus macaques provides an important model system for hcmv pathogenesis due to the genetic similarity between the viruses. in this report, seventeen rhcmv mirnas were identified using next generation sequencing. in fibroblasts, rhcm ...201222305624
species specificity of protein kinase r antagonism by cytomegalovirus trs1 genes.the host antiviral protein kinase r (pkr) has rapidly evolved during primate evolution, likely in response to challenges posed by many different viral antagonists, such as the trs1 gene of cytomegaloviruses (cmvs). in turn, viral antagonists have adapted to changes in pkr. as a result of this "arms race," modern trs1 alleles in cmvs may function differently in cells derived from alternative species. we have previously shown that human cmv trs1 (hutrs1) blocks the pkr pathway and rescues replicat ...201222278235
reevaluation of the coding potential and proteomic analysis of the bac-derived rhesus cytomegalovirus strain 68-1.cytomegaloviruses are highly host restricted, resulting in cospeciation with their hosts. as a natural pathogen of rhesus macaques (rm), rhesus cytomegalovirus (rhcmv) has therefore emerged as a highly relevant experimental model for pathogenesis and vaccine development due to its close evolutionary relationship to human cmv (hcmv). most in vivo experiments performed with rhcmv employed strain 68-1 cloned as a bacterial artificial chromosome (bac). however, the complete genome sequence of the 68 ...201222718821
host immune responses to a viral immune modulating protein: immunogenicity of viral interleukin-10 in rhesus cytomegalovirus-infected rhesus macaques.considerable evidence has accumulated that multiple viruses, bacteria, and protozoa manipulate interleukin-10 (il-10)-mediated signaling through the il-10 receptor (il-10r) in ways that could enable establishment of a persistent microbial infection. this suggests that inhibition of pathogen targeting of il-10/il-10r signaling could prevent microbial persistence. human cytomegalovirus (hcmv) and rhesus cytomegalovirus (rhcmv) express a viral interleukin-10 (cmvil-10 and rhcmvil-10, respectively) ...201222655082
patterns of acute rhesus cytomegalovirus (rhcmv) infection predict long-term rhcmv infection.we previously reported that long-term rhesus cytomegalovirus (rhcmv) excretion in infected macaques was related to ul/b' coding content. acute biopsy specimens of the inoculation sites from the previous study have now been analyzed to determine whether there were acute phenotypic predictors of long-term rhcmv infection. only in animals displaying acute endothelial tropism and neutrophilic inflammation was rhcmv excretion detected. the results imply that vaccinating against these early viral dete ...201222491451
open reading frames carried on ul/b' are implicated in shedding and horizontal transmission of rhesus cytomegalovirus in rhesus monkeys.implicit with the use of animal models to test human cytomegalovirus (hcmv) vaccines is the assumption that the viral challenge of vaccinated animals reflects the anticipated virus-host interactions following exposure of vaccinated humans to hcmv. variables of animal vaccine studies include the route of exposure to and the titer of challenge virus, as well as the genomic coding content of the challenge virus. this study was initiated to provide a better context for conducting vaccine trials with ...201121389128
profound early control of highly pathogenic siv by an effector memory t-cell vaccine.the acquired immunodeficiency syndrome (aids)-causing lentiviruses human immunodeficiency virus (hiv) and simian immunodeficiency virus (siv) effectively evade host immunity and, once established, infections with these viruses are only rarely controlled by immunological mechanisms. however, the initial establishment of infection in the first few days after mucosal exposure, before viral dissemination and massive replication, may be more vulnerable to immune control. here we report that siv vacci ...201121562493
Design and Analysis of Rhesus Cytomegalovirus IL-10 Mutants as a Model for Novel Vaccines against Human Cytomegalovirus.Human cytomegalovirus (HCMV) expresses a viral ortholog (CMVIL-10) of human cellular interleukin-10 (cIL-10). Despite only ~26% amino acid sequence identity, CMVIL-10 exhibits comparable immunosuppressive activity with cIL-10, attenuates HCMV antiviral immune responses, and contributes to lifelong persistence within infected hosts. The low sequence identity between CMVIL-10 and cIL-10 suggests vaccination with CMVIL-10 may generate antibodies that specifically neutralize CMVIL-10 biological acti ...201122132227
the cytoplasmic domain of rhesus cytomegalovirus rh178 interrupts translation of major histocompatibility class i leader peptide-containing proteins prior to translocation.cytomegalovirus (cmv) efficiently evades many host immune defenses and encodes a number of proteins that prevent antigen presentation by major histocompatibility complex class i (mhc-i) molecules in order to evade recognition and killing of infected cells by cytotoxic cd8(+) t cells. we recently showed that rhesus cmv-specific rh178 intercepts mhc-i protein translation before interference of mhc-i maturation by homologues of the human cmv us6 family. here, we demonstrate that rh178 localizes to ...201121715474
isolation and characterization of cynomolgus macaque (macaca fascicularis) cytomegalovirus (cycmv).cynomolgus macaques have been widely used as an animal model in preclinical biomedical research and are becoming more popular among hiv/siv vaccine researchers. here we report the isolation and characterization of a cytomegalovirus from cynomolgus macaques (cycmv). cycmv was isolated from a healthy captive-bred 4-year-old cynomolgus macaque of filipino origin. the virus was identified by its characteristic growth properties in cell culture, ultrastructural morphology and sequence of viral dna po ...201121272907
vaccine-induced control of viral shedding following rhesus cytomegalovirus challenge in rhesus macaques.the use of animal models of human cytomegalovirus (hcmv) infection is critical to refine hcmv vaccine candidates. previous reports have demonstrated that immunization of rhesus monkeys against rhesus cytomegalovirus (rhcmv) can reduce both local and systemic replication of rhcmv following experimental rhcmv challenge. these studies used prime/boost combinations of dna expression plasmids alone or dna priming and boosting with either inactivated virion particles or modified vaccinia virus ankara ...201021191005
characterization of the betaherpesviral pul69 protein family reveals binding of the cellular mrna export factor uap56 as a prerequisite for stimulation of nuclear mrna export and for efficient viral replication.ul69 of human cytomegalovirus (hcmv) encodes a pleiotropic transactivator protein and has a counterpart in every member of the herpesviridae family thus far sequenced. however, little is known about the conservation of the functions of the nuclear phosphoprotein pul69 in the homologous proteins of other betaherpesviruses. therefore, eukaryotic expression vectors were constructed for pc69 of chimpanzee cytomegalovirus, prh69 of rhesus cytomegalovirus, pm69 of murine cytomegalovirus, pu42 of human ...201021147923
attenuation of innate immunity by cytomegalovirus il-10 establishes a long-term deficit of adaptive antiviral immunity.human cytomegalovirus (hcmv) and many other pathogens exploit the il-10 pathway, as part of their infectious cycle, either through their own encoded il-10 (hcmvil-10 for hcmv) or manipulation of the cellular il-10 signaling cascade. based on the in vitro demonstrations of its pleiotropic and cell type-dependent modulatory nature, hcmvil-10 could profoundly attenuate host immunity, facilitating the establishment and maintenance of a persistent infection in an immune-competent host. to investigate ...201021149711
[development of the pcr-test system for detection primate betaherpesvirinae].a pcr-test system for detection of primate betaherpesvirinae viruses was developed. using alignment of complete genome of human, chimpanzee, and macaque rhesus cytomegalovirus conserve regions of viral genes were found. the oligonucleotide primers for consensus conserve regions of cmv ul56 gene were developed. the conditions of pcr were optimized and primer specificity for cytomegaloviruses of different primate species was confirmed.201020882773
rhesus and human cytomegalovirus glycoprotein l are required for infection and cell-to-cell spread of virus but cannot complement each other.rhesus cytomegalovirus (rhcmv), the homolog of human cytomegalovirus (hcmv), serves as a model for understanding the pathogenesis of hcmv and for developing candidate vaccines. in order to develop a replication-defective virus as a vaccine candidate, we constructed rhcmv with glycoprotein l (gl) deleted. rhcmv gl was essential for viral replication, and virus with gl deleted could only replicate in cells expressing rhcmv gl. noncomplementing cells infected with rhcmv with gl deleted released int ...201021191007
systemic spironucleosis in 2 immunodeficient rhesus macaques (macaca mulatta).spironucleus spp are parasites of fish and terrestrial vertebrates, including mice and turkeys, that rarely cause extraintestinal disease. two rhesus macaques (macaca mulatta) were experimentally inoculated with simian immunodeficiency virus mac251. both progressed to simian acquired immune deficiency syndrome within 1 year of inoculation and developed systemic protozoal infections in addition to common opportunistic infections, including rhesus cytomegalovirus, rhesus lymphocryptovirus, and rhe ...201020351359
effector memory t cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge.the rapid onset of massive, systemic viral replication during primary hiv or simian immunodeficiency virus (siv) infection and the immune evasion capabilities of these viruses pose fundamental problems for vaccines that depend upon initial viral replication to stimulate effector t cell expansion and differentiation. we hypothesized that vaccines designed to maintain differentiated effector memory t cell (tem cell) responses at viral entry sites might improve efficacy by impairing viral replicati ...200919219024
prevalence of viremia and oral shedding of rhesus rhadinovirus and retroperitoneal fibromatosis herpesvirus in large age-structured breeding groups of rhesus macaques (macaca mulatta).we performed a cross-sectional study to estimate the prevalence of 2 gamma-2-herpesviruses, rhesus rhadinovirus (rrv) and retroperitoneal fibromatosis herpesvirus (rfhv), in breeding colonies of rhesus macaques. of 90 animals selected for sampling, 73 (81%) were positive for rrv, which was detected only in blood in 22 (24%), only in saliva in 15 (16%), and in both blood and saliva in 36 (40%). detection of rrv dna in blood and saliva was significantly higher in animals younger than 2 y. in compa ...200919712580
molecular characterization of the genome of duck enteritis virus.the genomic sequence of a strain of duck enteritis virus (dev) was determined and analyzed in this study. the size of its genome is 158,091 bp in length and the genome is predicted to encode 78 putative proteins and resembles the members of the alphaherpesvirinae in genomic organization and gene composition. the genome of the virus is composed of a unique long (ul) region, a unique short (us) region, a unique short internal repeat (irs) region and a unique short terminal repeat (trs) region. its ...200919595405
protein coding content of the ul)b' region of wild-type rhesus cytomegalovirus.a recent comparison of two rhesus cytomegalovirus (rhcmv) genomes revealed that the region at the right end of the u(l) genome component (u(l)b') undergoes genetic alterations similar to those observed in serially passaged human cytomegalovirus (hcmv). to determine the coding content of authentic wild-type rhcmv in this region, the u(l)b' sequence was amplified from virus obtained from naturally infected rhesus macaques without passage in vitro. a total of 24 open reading frames (orfs) potential ...200818068749
functional genetic analysis of rhesus cytomegalovirus: rh01 is an epithelial cell tropism factor.rhesus cytomegalovirus (rhcmv) is an emerging model for human cytomegalovirus (hcmv) pathogenesis that facilitates experimental cmv infection of a natural primate host closely related to humans. we have generated a library of rhcmv mutants with lesions in genes whose hcmv orthologues have been characterized as nonessential for replication in human fibroblasts, and we characterized their replication in rhesus fibroblasts and epithelial cells. the rhcmv mutants grew well in fibroblasts, as predict ...200818094178
signal peptide-dependent inhibition of mhc class i heavy chain translation by rhesus cytomegalovirus.the us2-11 region of human and rhesus cytomegalovirus encodes a conserved family of glycoproteins that inhibit mhc-i assembly with viral peptides, thus preventing cytotoxic t cell recognition. since hcmv lacking us2-11 is no longer able to block assembly and transport of mhc-i, we examined whether this is also observed for rhcmv lacking the corresponding region. unexpectedly, recombinant rhcmv lacking us2-11 was still able to inhibit mhc-i expression in infected fibroblasts, suggesting the prese ...200818833297
efficient replication of rhesus cytomegalovirus variants in multiple rhesus and human cell types.rhesus cytomegalovirus infection of rhesus macaques has emerged as a model for human cytomegalovirus pathogenesis. the ul128-ul131 locus of the human virus is a primary determinant for viral entry into epithelial cells, an important cell type during cytomegalovirus infection. rhesus cytomegalovirus strain 68-1 spreads slowly when grown in cultured rhesus epithelial cells, and it does not code for orfs corresponding to ul128 and the second exon of ul130. we repaired the ul128-ul131 locus of strai ...200819064925
rhesus cytomegalovirus a nonhuman primate model for the study of human cytomegalovirus.human cytomegalovirus (hcmv), a member of an ancient family of viruses (herpesviridae), has acquired the capacity to maintain a lifelong persistent infection within an immunocompetent host. since both primary and recurrent infections are generally subclinical, host antiviral immune responses are effective at limiting the pathogenic potential of hcmv. however, the fact that hcmv can persist in the presence of those protective immune responses indicates that host immunity is unable to prevent or e ...200819081492
a heterologous dna prime/protein boost immunization strategy for rhesus cytomegalovirus.a previous study in nonhuman primates demonstrated that genetic immunization against the rhesus cytomegalovirus phosphoprotein 65-2 (pp65-2) and glycoprotein b (gb) antigens both stimulated antigen-specific antibodies and cd8 t cell responses, and significantly reduced plasma viral loads following intravenous challenge with rhcmv. it was also noted in this study that weak cd4 t cell and neutralizing antibody responses were generated by dna alone. to broaden the type of immune responses, a dna pr ...200818760319
development of breeding populations of rhesus macaques (macaca mulatta) that are specific pathogen-free for rhesus cytomegalovirus.development of breeding colonies of rhesus macaques (macaca mulatta) that are specific pathogen-free (spf) for rhesus cytomegalovirus (rhcmv) is relatively straightforward and requires few modifications from current spf programs. infants separated from the dam at or within a few days of birth and cohoused with similarly treated animals remain rhcmv seronegative indefinitely, provided they are never directly or indirectly exposed to a rhcmv-infected monkey. by systematically cohousing seronegativ ...200819793455
evaluation of recombinant modified vaccinia ankara virus-based rhesus cytomegalovirus vaccines in rhesus macaques.a vaccine consisting of rhesus cytomegalovirus (rhcmv) pp65-2, gb and ie1 expressed via modified vaccinia ankara (mva) was evaluated in rhesus macaques with or without prior priming with expression plasmids for the same antigens. following two mva treatments, comparable levels of anti-gb, pp65-2 and neutralizing antibody responses, and pp65-2- and ie1-specific cellular immune responses were detected in both vaccinated groups. similar reductions in plasma peak viral loads were observed in these g ...200818196272
unique pattern of enzootic primate viruses in gibraltar macaques.because gibraltar's macaques (macaca sylvanus) have frequent contact with humans, we assayed 79 macaques for antibodies to enzootic primate viruses. all macaques were seronegative for herpesvirus b, simian t-cell lymphotropic virus, simian retrovirus, simian immunodeficiency virus, and rhesus cytomegalovirus. seroprevalence of simian foamy virus reached 88% among adult animals.200818598634
immunogenicity and protective efficacy of dna vaccines expressing rhesus cytomegalovirus glycoprotein b, phosphoprotein 65-2, and viral interleukin-10 in rhesus macaques.rhesus cytomegalovirus (rhcmv) infection of macaques exhibits strong similarities to human cmv (hcmv) persistence and pathogenesis. the immunogenicity of dna vaccines encoding three rhcmv proteins (a truncated version of glycoprotein b lacking the transmembrane region and endodomain [gbdeltatm], phosphoprotein 65-2 [pp65-2], and viral interleukin-10 [vil-10]) was evaluated in rhesus macaques. two groups of monkeys (four per group) were genetically immunized four times with a mixture of either pp ...200717108040
flow cytometric detection of degranulation reveals phenotypic heterogeneity of degranulating cmv-specific cd8+ t lymphocytes in rhesus macaques.flow-cytometric conditions for detection of lysosomal-associated membrane proteins (lamps) on the surface of recently degranulated cells were optimized for rhesus macaques and used to investigate the functional properties of rhesus cytomegalovirus (rhcmv)-specific cd8+ t lymphocytes with regards to cytotoxicity and interferon (ifn)-gamma secretion in six asymptomatic cmv-seropositive rhesus macaques. unlike humans, the rhesus macaque lamp-1 protein cd107a underwent little or no endocytosis over ...200717628586
temple monkeys and health implications of commensalism, kathmandu, nepal.the threat of zoonotic transmission of infectious agents at monkey temples highlights the necessity of investigating the prevalence of enzootic infectious agents in these primate populations. biological samples were collected from 39 rhesus macaques at the swoyambhu temple and tested by enzyme-linked immunosorbent assay, western blot, polymerase chain reaction, or combination of these tests for evidence of infection with rhesus cytomegalovirus (rhcmv), cercopithecine herpesvirus 1 (chv-1), simia ...200616707044
genomic sequence of rhesus cytomegalovirus 180.92: insights into the coding potential of rhesus cytomegalovirus.a pathogenic isolate of rhesus cytomegalovirus (rhcmv 180.92) was cloned, sequenced, and annotated. comparisons with the published rhcmv 68.1 genome revealed 8 open reading frames (orfs) in isolate 180.92 that are absent in 68.1, 10 orfs in 68.1 that are absent in 180.92, and 34 additional orfs that were not previously annotated. most of the differences appear to be due to genetic rearrangements in both isolates from a region that is frequently altered in human cmv (hcmv) during in vitro passage ...200616571834
premature induction of an immunosuppressive regulatory t cell response during acute simian immunodeficiency virus infection.here we report the results of an investigation into the possibility that one mechanism responsible for the establishment of persistent human immunodeficiency virus infection is an early regulatory t (treg) cell response that blunts virus-specific responses. using the simian immunodeficiency virus (siv)-infected rhesus macaque model, we show that, indeed, viral replication and immune activation in lymphatic tissue drive a premature immunosuppressive response, with dramatic increases in the freque ...200616453267
simultaneous detection of antibodies to six nonhuman-primate viruses by multiplex microbead immunoassay.to maintain healthy nonhuman primates for use in biomedical research, animals are routinely screened for several infectious agents at most facilities. commonly, monkey serum samples are tested by conventional immunoassays, such as enzyme-linked immunosorbent assays (elisas) or western blotting, for antibodies to specific infectious agents. for testing for antibodies against multiple agents in each sample, conventional immunoassays are laborious and time-consuming. more efficient immunoassays are ...200616425999
characterization and immunological analysis of the rhesus cytomegalovirus homologue (rh112) of the human cytomegalovirus ul83 lower matrix phosphoprotein (pp65).rhesus cytomegalovirus (rhcmv) contains two open reading frames (rh111 and rh112) that encode proteins homologous to the phosphoprotein 65 (pp65) of the human cytomegalovirus (hcmv) ul83 gene. as hcmv pp65 elicits protective immune responses in infected humans and represents an important vaccination target, one rhcmv homologue of hcmv pp65, pp65-2 (rh112), was characterized and analysed for its ability to induce host immune responses. similar to its hcmv counterpart, rhcmv pp65-2 was expressed a ...200616528025
rhesus cytomegalovirus particles prevent activation of interferon regulatory factor 3.one of the most important innate host defense mechanisms against viral infection is the induction of interferon (ifn)-stimulated genes (isgs). immediately upon entry, viruses activate interferon-regulatory factor 3 (irf3), as well as nuclear factor kappab (nf-kappab), which transactivate a subset of isgs, proinflammatory genes, as well as ifn genes. most large dna viruses exhibit countermeasures against induction of this response. however, whereas human cytomegalovirus (hcmv) inhibits ifn-depend ...200515858025
rhesus cytomegalovirus contains functional homologues of us2, us3, us6, and us11.human cytomegalovirus (hcmv) is a paradigm for mechanisms subverting antigen presentation by major histocompatibility complex (mhc) molecules. due to its limited host range, hcmv cannot be studied in animals. thus, the in vivo importance of inhibiting antigen presentation for the establishment and maintenance of infection with hcmv is unknown. rhesus cytomegalovirus (rhcmv) is an emerging animal model that shares many of the features of hcmv infection. the recent completion of the genomic sequen ...200515827193
rhesus brain microvascular endothelial cells are permissive for rhesus cytomegalovirus infection.endothelial cells (ec) are an important cell type for human cytomegalovirus (cmv) pathogenesis. to characterize better the role of ec in primate cmv natural history, rhesus macaque microvascular ec (mvec) were purified from fetal brain and analysed for infectivity by rhesus cytomegalovirus (rhcmv). rhesus brain mvec (brmvec) in culture were positive for von willebrand factor and cd105 expression, uptake of acetylated low-density lipoprotein, and formation of capillary-like tubules on matrigel, a ...200515722513
a cyclooxygenase-2 homologue encoded by rhesus cytomegalovirus is a determinant for endothelial cell tropism.cyclooxygenase-2 (cox-2) is a cellular enzyme in the eicosanoid synthetic pathway that mediates the synthesis of prostaglandins from arachidonic acid. the eicosanoids function as critical regulators of a number of cellular processes, including the acute and chronic inflammatory response, hemostasis, and the innate immune response. human cytomegalovirus (hcmv), which does not encode a viral cox-2 isoform, has been shown to induce cellular cox-2 expression. importantly, although the precise role o ...200415507640
rhesus cytomegalovirus is similar to human cytomegalovirus in susceptibility to benzimidazole nucleosides.rhesus and human cytomegalovirus (rhcmv and hcmv, respectively) exhibit comparable inhibition by benzimidazole nucleosides, including 2,5,6-trichloro-(1-beta-d-ribofuranosyl)benzimidazole (tcrb), and pyrrolo[2,3-d]pyrimidines. the two hcmv protein targets of tcrb, ul89 and ul56, are highly conserved with their rhcmv homologues. these data indicate that infection of rhesus macaques with rhcmv represents a useful model to test novel anti-hcmv drugs.200415215146
characterization of the rhesus cytomegalovirus us28 locus.human cytomegalovirus (cmv) us28 (and the related open reading frame [orf] us27) are g-protein-coupled receptor homologs believed to play a role in viral pathogenesis. in vitro, us28 has been shown to bind and internalize ligands, as well as activate intracellular signaling in response to certain chemokines, and to initiate the migration of smooth muscle cells to chemokine gradients. to assess the role of us28 in vivo, we examined the rhesus model and sequenced and characterized the rhesus cmv u ...200312970425
prevalence of antibodies to selected viruses in a long-term closed breeding colony of rhesus macaques (macaca mulatta) in brazil.the rhesus macaque breeding colony of the oswaldo cruz foundation (fiocruz) was established in 1932 from a founding stock of 100 animals. this population has remained closed to new animal introductions for almost 70 years. a serologic survey was performed to determine the prevalence of antibodies to selected viruses as a first approach to identifying viral pathogens endemic in this population. banked serum samples were tested for antibodies to simian immunodeficiency virus (siv), simian t-lympho ...200312619046
complete sequence and genomic analysis of rhesus cytomegalovirus.the complete dna sequence of rhesus cytomegalovirus (rhcmv) strain 68-1 was determined with the whole-genome shotgun approach on virion dna. the rhcmv genome is 221,459 bp in length and possesses a 49% g+c base composition. the genome contains 230 potential open reading frames (orfs) of 100 or more codons that are arranged colinearly with counterparts of previously sequenced betaherpesviruses such as human cytomegalovirus (hcmv). of the 230 rhcmv orfs, 138 (60%) are homologous to known hcmv prot ...200312767982
antibody responses to rhesus cytomegalovirus glycoprotein b in naturally infected rhesus macaques.rhesus cytomegalovirus (rhcmv) exhibits strong parallels with human cmv (hcmv) in terms of nucleic and amino acid identities, natural history, and mechanisms of persistence and pathogenesis in its natural host, rhesus macaques (macaca mulatta). to determine whether this non-human primate model would be useful to assess vaccine strategies for hcmv, host immune responses to rhcmv glycoprotein b (gb) were evaluated in rhcmv-infected monkeys. total protein extracts were prepared from cells transient ...200314645918
cloning of the full-length rhesus cytomegalovirus genome as an infectious and self-excisable bacterial artificial chromosome for analysis of viral pathogenesis.rigorous investigation of many functions encoded by cytomegaloviruses (cmvs) requires analysis in the context of virus-host interactions. to facilitate the construction of rhesus cmv (rhcmv) mutants for in vivo studies, a bacterial artificial chromosome (bac) containing an enhanced green fluorescent protein (egfp) cassette was engineered into the intergenic region between unique short 1 (us1) and us2 of the full-length viral genome by cre/lox-mediated recombination. infectious virions were recov ...200312692210
differential detection of b virus and rhesus cytomegalovirus in rhesus macaques.non-human primate herpesviruses establish and maintain a lifelong persistent infection in immunocompetent hosts in the absence of clinical signs of disease. a fundamental issue for understanding the natural history of non-human primate herpesviruses is whether the viruses are maintained in a truly latent state or one characterized by a low level of chronic expression. to address this issue, a real-time pcr assay was developed to quantify cercopithecine herpesvirus type 1 (b virus) dna in mucosal ...200312533703
a recombinant rhesus cytomegalovirus expressing enhanced green fluorescent protein retains the wild-type phenotype and pathogenicity in fetal macaques.to facilitate identification of rhesus cytomegalovirus (rhcmv)-infected cells, a recombinant virus expressing enhanced green fluorescent protein (egfp), designated rhcmv-egfp, was constructed. an expression cassette for egfp under the control of the simian virus 40 (sv40) early promoter was inserted into the intergenic region between unique short 1 (us1) and us2 of the rhcmv genome by homologous recombination. rhcmv-egfp exhibited comparable growth kinetics to that of wild-type virus in rhesus f ...200212186931
experimental coinfection of rhesus macaques with rhesus cytomegalovirus and simian immunodeficiency virus: pathogenesis.human cytomegalovirus (hcmv) possesses low pathogenic potential in an immunocompetent host. in the immunosuppressed host, however, a wide spectrum of infection outcomes, ranging from asymptomatic to life threatening, can follow either primary or nonprimary infection. the variability in the manifestations of hcmv infection in immunosuppressed individuals implies that there is a threshold of host antiviral immunity that can effectively limit disease potential. we used a nonhuman primate model of c ...200212097580
replication of rhesus cytomegalovirus in life-expanded rhesus fibroblasts expressing human telomerase.the kinetics of rhesus cytomegalovirus (rhcmv) infection were compared in primary and telomerase-immortalized (telo-) rhesus fibroblasts (rf). equivalent viral titers were achieved with both cell types. however, the production of infectious virions was slightly faster and plaque size was larger in telo-rf, compared with primary cells. comparable rhcmv growth curves and viral susceptibility were observed using telo-rf passaged for different time periods in culture, whereas the ability of primary ...200212088823
primate cytomegaloviruses encode and express an il-10-like protein.an open reading frame (orf) with homology to interleukin-10 (il-10) has been identified in rhesus cytomegalovirus (rhcmv). the il-10-like protein is generated from a multispliced, polyadenylated early gene transcript encompassing part of the corresponding ul111a orf of human cmv (hcmv). immunological analyses confirm expression of the il-10-like protein both in tissue culture and in rhcmv-infected rhesus macaques. conserved orfs were subsequently identified in human, baboon, and african green mo ...200010704336
pathogenesis of experimental rhesus cytomegalovirus infection.human cytomegalovirus (hcmv) establishes and maintains a lifelong persistence following infection in an immunocompetent host. the determinants of a stable virus-host relationship are poorly defined. a nonhuman primate model for hcmv was used to investigate virological and host parameters of infection in a healthy host. juvenile rhesus macaques (macaca mulatta) were inoculated with rhesus cytomegalovirus (rhcmv), either orally or intravenously (i.v. ), and longitudinally necropsied. none of the a ...199910516066
the relationship of personality dimensions in adult male rhesus macaques to progression of simian immunodeficiency virus disease.studies of nonhuman primate personality have suggested that physiological correlates of relevant behavioral dimensions exist. the present study examined personality using techniques similar to those employed in human personality research. adult male rhesus monkeys were each rated on 25 adjectives while living in their natal groups. approximately 1.5 years later, 18 animals were inoculated with the simian immunodeficiency virus (siv) and exposed to socially stable or socially unstable conditions. ...199910373278
immunohistochemical studies of productive rhesus cytomegalovirus infection in rhesus monkeys (macaca mulatta) infected with simian immunodeficiency virus.in humans infected with the human immunodeficiency virus (hiv), clinical disease due to human cytomegalovirus (hcmv) infection is one of the aids-defining diseases; hcmv is the most common opportunistic infection found postmortem. histologically, the typical lesions are characterized by "owl's eye cells." in rhesus monkeys infected with simian immunodeficiency virus (siv), comparable lesions are caused by an infection with the rhesus cmv (rhcmv). the aim of this study was to investigate the inci ...19999921756
characterization of rhesus cytomegalovirus genes associated with anti-viral susceptibility.studies were initiated to determine whether rhesus cytomegalovirus (rhcmv)-infected macaques could serve as an animal model for evaluating anti-cmv compounds, as macaques have a naturally occurring cmv that is similar to human cmv (hcmv). utilizing plaque reduction assays, rhcmv was tested to anti-viral susceptibility. by these assays. rhcmv displayed anti-viral susceptibility to ganciclovir at a 50% effective dose (ed50) of 0.8 microm, acyclovir at an ed50 of 15 microm, and foscarnet at an ed50 ...19989454707
neuropathogenesis induced by rhesus cytomegalovirus in fetal rhesus monkeys (macaca mulatta).rhesus cytomegalovirus (rhcmv) infection of rhesus macaques offers opportunities to analyze mechanisms of cmv pathogenesis in a primate species. four fetal rhesus monkeys were inoculated intraperitoneally with rhcmv early in the second trimester, and pregnancies were terminated by hysterotomy during the third trimester. three fetuses had evidence of severe cmv disease, including intrauterine growth restriction, ventriculomegaly, microcephaly, lissencephaly, and extensive degenerative changes of ...19989466534
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