| simian varicella virus pathogenesis. | because varicella zoster virus (vzv) is an exclusively human pathogen, the development of an animal model is necessary to study pathogenesis, latency, and reactivation. the pathological, virological, and immunological features of simian varicella virus (svv) infection in nonhuman primates are similar to those of vzv infection in humans. both natural infection of cynomolgus and african green monkeys as well as intrabronchial inoculation of rhesus macaques with svv provide the most useful models t ... | 2010 | 20186611 |
| simian varicella virus gene expression during acute and latent infection of rhesus macaques. | varicella zoster virus (vzv) is a neurotropic α-herpesvirus that causes chickenpox during primary infection and establishes latency in sensory ganglia. reactivation of vzv results in herpes zoster and other neurological complications. our understanding of the vzv transcriptome during acute and latent infection in immune competent individuals remains incomplete. infection of rhesus macaques with the homologous simian varicella virus (svv) recapitulates the hallmarks of vzv infection. we therefore ... | 2011 | 22052378 |
| t-cell infiltration correlates with cxcl10 expression in ganglia of cynomolgus macaques with reactivated simian varicella virus. | ganglia of monkeys with reactivated simian varicella virus (svv) contained more cd8 than cd4 t cells around neurons. the abundance of cd8 t cells was greater less than 2 months after reactivation than that at later times and correlated with that of cxcl10 rna but not with those of svv protein or open reading frame 61 (orf61) antisense rna. cxcl10 rna colocalized with t-cell clusters. after svv reactivation, transient t-cell infiltration, possibly mediated by cxcl10, parallels varicella zoster vi ... | 2012 | 23269790 |
| simian varicella virus: molecular virology. | simian varicella virus (svv) is a primate herpesvirus that is closely related to varicella-zoster virus (vzv), the causative agent of varicella (chickenpox) and herpes zoster (shingles). epizootics of simian varicella occur sporadically in facilities housing old world monkeys. this review summarizes the molecular properties of svv. the svv and vzv genomes are similar in size, structure, and gene arrangement. the 124.5 kilobase pair (kbp) svv genome includes a 104.7 kbp long component covalently ... | 2010 | 20369316 |
| recombinant varicella vaccines induce neutralizing antibodies and cellular immune responses to siv and reduce viral loads in immunized rhesus macaques. | the development of an effective aids vaccine remains one of the highest priorities in hiv research. the live, attenuated varicella-zoster virus (vzv) oka vaccine, safe and effective for prevention of chickenpox and zoster, also has potential as a recombinant vaccine against other pathogens, including human immunodeficiency virus (hiv). the simian varicella model, utilizing simian varicella virus (svv), offers an approach to evaluate recombinant varicella vaccine candidates. recombinant svv (rsvv ... | 2010 | 20654666 |
| latent simian varicella virus reactivates in monkeys treated with tacrolimus with or without exposure to irradiation. | simian varicella virus (svv) infection of primates resembles human varicella-zoster virus (vzv) infection. after primary infection, svv becomes latent in ganglia and reactivates after immunosuppression or social and environmental stress. herein, natural svv infection was established in 5 cynomolgus macaques (cynos) and 10 african green (ag) monkeys. four cynos were treated with the immunosuppressant tacrolimus (80 to 300 μg/kg/day) for 4 months and 1 was untreated (group 1). four ag monke ... | 2010 | 20822371 |
| characterization of the immune response in ganglia after primary simian varicella virus infection. | primary simian varicella virus (svv) infection in non-human primates causes varicella, after which the virus becomes latent in ganglionic neurons and reactivates to cause zoster. the host response in ganglia during establishment of latency is ill-defined. ganglia from five african green monkeys (agms) obtained at 9, 13, and 20 days post-intratracheal svv inoculation (dpi) were analyzed by ex vivo flow cytometry, immunohistochemistry, and in situ hybridization. ganglia at 13 and 20 dpi exhibited ... | 2015 | 26676825 |
| simian varicella virus infection of chinese rhesus macaques produces ganglionic infection in the absence of rash. | varicella-zoster virus (vzv) causes varicella (chickenpox), becomes latent in ganglia along the entire neuraxis, and may reactivate to cause herpes zoster (shingles). vzv may infect ganglia via retrograde axonal transport from infected skin or through hematogenous spread. simian varicella virus (svv) infection of rhesus macaques provides a useful model system to study the pathogenesis of human vzv infection. to dissect the virus and host immune factors during acute svv infection, we analyzed fou ... | 2012 | 22399159 |
| robust gene expression changes in the ganglia following subclinical reactivation in rhesus macaques infected with simian varicella virus. | varicella zoster virus (vzv) causes varicella during acute infection and establishes latency in the sensory ganglia. reactivation of vzv results in herpes zoster, a debilitating and painful disease. it is believed that vzv reactivates due to a decline in cell-mediated immunity; however, the roles that cd4 versus cd8 t cells play in the prevention of herpes zoster remain poorly understood. to address this question, we used a well-characterized model of vzv infection where rhesus macaques are intr ... | 2017 | 28321697 |
| myelodysplasia in 2 pig-tailed macaques (macaca nemestrina) associated with retroviral vector-mediated insertional mutagenesis and overexpression of hoxb4. | gammaretroviral vectors are an efficient means to effect gene therapy. however, genotoxicity from insertion at nonrandom sites can confer a competitive advantage to transduced cells, resulting in clonal proliferation or neoplasia. six pig-tailed macaques (macaca nemestrina) underwent total body irradiation and reconstitution with autologous stem cells genetically modified by a gammaretroviral vector overexpressing hoxb4. two animals were euthanized owing to irradiation- or transplantation-associ ... | 2010 | 20870955 |
| acute simian varicella virus infection causes robust and sustained changes in gene expression in the sensory ganglia. | primary infection with varicella-zoster virus (vzv), a neurotropic alphaherpesvirus, results in varicella. vzv establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster. the relationship between vzv and its host during acute infection in the sensory ganglia is not well understood due to limited access to clinical specimens. intrabronchial inoculation of rhesus macaques with simian varicella virus (svv) recapitulates the hallmarks of vzv infection in human ... | 2016 | 27681124 |
| varicella viruses inhibit interferon-stimulated jak-stat signaling through multiple mechanisms. | varicella zoster virus (vzv) causes chickenpox in humans and, subsequently, establishes latency in the sensory ganglia from where it reactivates to cause herpes zoster. infection of rhesus macaques with simian varicella virus (svv) recapitulates vzv pathogenesis in humans thus representing a suitable animal model for vzv infection. while the type i interferon (ifn) response has been shown to affect vzv replication, the virus employs counter mechanisms to prevent the induction of anti-viral ifn s ... | 2015 | 25973608 |
| impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques. | in this study we examined the effects of non-myeloablative total body irradiation (tbi) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. our results show that the administration of cyclosporin a or tacrolimus without radiotherapy did not result in lymphopenia. the addition of tbi to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. dendritic cell (dc) numbers in whol ... | 2015 | 25902927 |
| bacterial artificial chromosome derived simian varicella virus is pathogenic in vivo. | varicella zoster virus (vzv) is a neurotropic alphaherpesvirus that infects humans and results in chickenpox and herpes zoster. a number of vzv genes remain functionally uncharacterized and since vzv is an obligate human pathogen, rigorous evaluation of vzv mutants in vivo remains challenging. simian varicella virus (svv) is homologous to vzv and svv infection of rhesus macaques (rm) closely mimics vzv infection of humans. recently the svv genome was cloned as a bacterial artificial chromosome ( ... | 2013 | 24010815 |
| genome-wide analysis of t cell responses during acute and latent simian varicella virus infections in rhesus macaques. | varicella zoster virus (vzv) is the etiological agent of varicella (chickenpox) and herpes zoster (hz [shingles]). clinical observations suggest that vzv-specific t cell immunity plays a more critical role than humoral immunity in the prevention of vzv reactivation and development of herpes zoster. although numerous studies have characterized t cell responses directed against select vzv open reading frames (orfs), a comprehensive analysis of the t cell response to the entire vzv genome has not y ... | 2013 | 23986583 |
| gexps multiplex pcr analysis of the simian varicella virus transcriptome in productively infected cells in culture and acutely infected ganglia. | simian varicella zoster virus (svv) infection of non-human primates serves as a model to study varicella zoster virus (vzv) infection and pathogenesis in humans. while macroarray analysis detected all 69 predicted unique open reading frames (orfs) in svv-infected cells in culture, it lacked the sensitivity to detect the low-abundance transcripts expressed in latently infected monkey ganglia. recently, a multiplex rt-pcr assay using the genomelab genetic analysis system (gexps) identified 10 vzv ... | 2013 | 23769859 |
| age and immune status of rhesus macaques impact simian varicella virus gene expression in sensory ganglia. | simian varicella virus (svv) infection of rhesus macaques (rms) recapitulates the hallmarks of varicella-zoster virus (vzv) infection of humans, including the establishment of latency within the sensory ganglia. various factors, including age and immune fitness, influence the outcome of primary vzv infection, as well as reactivation resulting in herpes zoster (hz). to increase our understanding of the role of lymphocyte subsets in the establishment of viral latency, we analyzed the latent svv tr ... | 2013 | 23698305 |
| t-cell tropism of simian varicella virus during primary infection. | varicella-zoster virus (vzv) causes varicella, establishes a life-long latent infection of ganglia and reactivates to cause herpes zoster. the cell types that transport vzv from the respiratory tract to skin and ganglia during primary infection are unknown. clinical, pathological, virological and immunological features of simian varicella virus (svv) infection of non-human primates parallel those of primary vzv infection in humans. to identify the host cell types involved in virus dissemination ... | 2013 | 23675304 |
| simian varicella virus gene 28 and 29 promoters share a common upstream stimulatory factor-binding site and are induced by ie62 transactivation. | simian varicella virus (svv) is a neurotropic alphaherpesvirus that causes a natural, varicella-like disease in non-human primates. after resolution of the primary disease, svv, like its human counterpart, varicella-zoster virus (vzv), establishes latent infection in the neural ganglia of the host. in this study, gene expression of svv open reading frames (orfs) 28 and 29, which encode the viral dna polymerase and dna-binding protein, respectively, was characterized during lytic infection of ver ... | 2006 | 16690914 |
| cercopithecine herpesvirus 9 (simian varicella virus) infection after total-body irradiation in a rhesus macaque (macaca mulatta). | this case report describes a rhesus macaque (macaca mulatta; male; age, 5 y; weight, 6.7 kg) with anorexia, dehydration, lethargy, ataxia, and generalized skin rashes that occurred 30 d after total-body irradiation at 6.5 gy ((60)co γ-rays). physical examination revealed pale mucus membranes, a capillary refill time of 4 s, heart rate of 180 bpm. and respirations at 50 breaths per minute. diffuse multifocal maculopapulovesicular rashes were present on the body, including mucocutaneous junctions. ... | 2016 | 27053570 |
| immunological evasion of immediate-early varicella zoster virus proteins. | the varicella zoster virus (vzv) causes the childhood disease commonly known as chickenpox and can later in life reactivate as herpes zoster. the adaptive immune system is known to play an important role in suppressing vzv reactivation. a central aspect of this system is the presentation of vzv-derived peptides by the major histocompatibility complex (mhc) proteins. here, we investigate if key vzv proteins have evolved their amino acid sequence to avoid presentation by mhc based on predictive mo ... | 2016 | 27020058 |
| simian varicella virus gene 61 encodes a viral transactivator but is non-essential for in vitro replication. | simian varicella virus (svv) is closely related to varicella-zoster virus (vzv), the causative agent of chickenpox and shingles. the svv and vzv gene 61 polypeptides are homologs of the hsv-1 icp0, a viral transactivator which appears to play a role in viral latency and reactivation. in this study, the molecular properties of the svv 61 were characterized. the svv open reading frame (orf) 61 encodes a 54.1-kda polypeptide with 37% amino acid identity to the vzv 61. homology to the hsv-1 icp-0 is ... | 2007 | 17115302 |
| abortive intrabronchial infection of rhesus macaques with varicella-zoster virus provides partial protection against simian varicella virus challenge. | varicella-zoster virus (vzv) is a human neurotropic alphaherpesvirus and the etiological agent of varicella (chickenpox) and herpes zoster (hz, shingles). previously, inoculation of monkeys via the subcutaneous, intratracheal, intravenous, or oral-nasal-conjunctival routes did not recapitulate all the hallmarks of vzv infection, including varicella, immunity, latency, and reactivation. intrabronchial inoculation of rhesus macaques (rms) with simian varicella virus (svv), a homolog of vzv, recapi ... | 2015 | 25410871 |
| pathogenesis of varicelloviruses in primates. | varicelloviruses in primates comprise the prototypic human varicella-zoster virus (vzv) and its non-human primate homologue, simian varicella virus (svv). both viruses cause varicella as a primary infection, establish latency in ganglionic neurons and reactivate later in life to cause herpes zoster in their respective hosts. vzv is endemic worldwide and, although varicella is usually a benign disease in childhood, vzv reactivation is a significant cause of neurological disease in the elderly and ... | 2015 | 25255989 |
| intrabronchial infection of rhesus macaques with simian varicella virus results in a robust immune response in the lungs. | varicella-zoster virus (vzv) is the etiological agent of varicella (chickenpox) and herpes zoster (shingles). primary vzv infection is believed to occur via the inhalation of virus either in respiratory droplets or from shedding varicella lesions or by direct contact with infectious vesicular fluid. however, the ensuing immune response in the lungs remains incompletely understood. we have shown that intrabronchial inoculation of rhesus macaques with simian varicella virus (svv), a homolog of vzv ... | 2014 | 25142604 |
| robust pro-inflammatory and lesser anti-inflammatory immune responses during primary simian varicella virus infection and reactivation in rhesus macaques. | simian varicella virus (svv) infection of non-human primates models human varicella zoster virus (vzv) infection. assessment of cell signaling immune responses in monkeys after primary svv infection, after immunosuppression and during reactivation revealed strong pro-inflammatory responses and lesser anti-inflammatory components during varicella and reactivation. pro-inflammatory mediators elevated during varicella included interferon-gamma (ifn-γ), interleukin (il)-6, monocyte chemoattractant p ... | 2014 | 25139181 |
| t cells increase before zoster and pd-1 expression increases at the time of zoster in immunosuppressed nonhuman primates latently infected with simian varicella virus. | like varicella zoster virus in humans, simian varicella virus (svv) becomes latent in ganglionic neurons along the entire neuraxis and reactivates in immunosuppressed monkeys. five rhesus macaques were inoculated with svv; 142 days later (latency), four monkeys were immunosuppressed, and t cells were analyzed for naïve, memory, and effector phenotypes and expression of programmed death receptor-1 (pd-1; t cell exhaustion). all t cell subsets decreased during immunosuppression and except for cd8 ... | 2014 | 24549971 |
| reactivation of simian varicella virus in rhesus macaques after cd4 t cell depletion. | rhesus macaques intrabronchially inoculated with simian varicella virus (svv), the counterpart of human varicella-zoster virus (vzv), developed primary infection with viremia and rash, which resolved upon clearance of viremia, followed by the establishment of latency. to assess the role of cd4 t cell immunity in reactivation, monkeys were treated with a single 50-mg/kg dose of a humanized monoclonal anti-cd4 antibody; within 1 week, circulating cd4 t cells were reduced from 40 to 60% to 5 to 30% ... | 2019 | 30404798 |
| 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. | 2018 | 30264877 |
| distinct transcriptional responses to fatal ebola virus infection in cynomolgus and rhesus macaques suggest species-specific immune responses. | ebola virus (ebov) is a negative single-stranded rna virus within the filoviridae family and the causative agent of ebola virus disease (evd). nonhuman primates (nhps), including cynomolgus and rhesus macaques, are considered the gold standard animal model to interrogate mechanisms of ebov pathogenesis. however, despite significant genetic similarity (>90%), nhp species display different clinical presentation following ebov infection, notably a ∼1-2 days delay in disease progression. consequentl ... | 2021 | 34112056 |
| intratracheal inoculation of human varicella zoster virus (vzv; mav strain) vaccine successfully induced vzv igg antibodies in rhesus monkeys. | the objective of this study was to investigate whether the use of live attenuated varicella zoster virus (vzv) mav vaccination can efficiently induce vzv antibody production in naive rhesus monkeys as an approach to prevent simian varicella virus (svv) reactivation in animals immunosuppressed for transplantation studies. | 2021 | 34022964 |
| comprehensive analysis of varicella-zoster virus proteins using a new monoclonal antibody collection. | varicella-zoster virus (vzv) is the etiological agent of chickenpox and shingles. due to the virus's restricted host and cell type tropism and the lack of tools for vzv proteomics, it is one of the least-characterized human herpesviruses. we generated 251 monoclonal antibodies (mabs) against 59 of the 71 (83%) currently known unique vzv proteins to characterize vzv protein expression in vitro and in situ. using this new set of mabs, 44 viral proteins were detected by western blotting (wb) and in ... | 2013 | 23596286 |
| animal models of varicella zoster virus infection. | primary infection with varicella zoster virus (vzv) results in varicella (chickenpox) followed by the establishment of latency in sensory ganglia. declining t cell immunity due to aging or immune suppressive treatments can lead to vzv reactivation and the development of herpes zoster (hz, shingles). hz is often associated with significant morbidity and occasionally mortality in elderly and immune compromised patients. there are currently two fda-approved vaccines for the prevention of vzv: variv ... | 2013 | 25437040 |
| attenuation of the adaptive immune response in rhesus macaques infected with simian varicella virus lacking open reading frame 61. | varicella zoster virus (vzv) is a neurotropic alphaherpesvirus that causes chickenpox during primary infection and establishes latency in sensory ganglia. infection of rhesus macaques (rm) with the homologous simian varicella virus (svv) recapitulates hallmarks of vzv infection. we have shown that an antisense transcript of svv open reading frame 61 (orf61), a viral transactivator, was detected most frequently in latently infected rm sensory ganglia. in this study, we compared disease progressio ... | 2013 | 23221560 |
| increased cellular immune responses and cd4+ t-cell proliferation correlate with reduced plasma viral load in siv challenged recombinant simian varicella virus - simian immunodeficiency virus (rsvv-siv) vaccinated rhesus macaques. | an effective aids vaccine remains one of the highest priorities in hiv-research. our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rsvv) vector - simian immunodeficiency virus (siv) envelope and gag genes, induced neutralizing antibodies and cellular immune responses to siv and also significantly reduced plasma viral loads following intravenous pathogenic challenge with sivmac251/cx1. | 2012 | 22889373 |
| the simian varicella virus orf a is expressed in infected cells but is non-essential for replication in cell culture. | the simian varicella virus (svv) genome encodes orf a, a truncated homolog of svv orf 4. the svv orf a was expressed as a 1.0-kb transcript in svv-infected vero cells. the orf a promoter was active in infected vero cells and was stimulated by the svv immediate-early gene orf 62 product (ie62), a viral transactivator of svv genes. the svv orf a did not transactivate svv ie, early, or late gene promoters in transfected vero cells and was unable to augment ie62-mediated transactivation of svv promo ... | 2012 | 22678718 |
| CD4 T cell immunity is critical for the control of simian varicella virus infection in a nonhuman primate model of VZV infection. | Primary infection with varicella zoster virus (VZV) results in varicella (more commonly known as chickenpox) after which VZV establishes latency in sensory ganglia. VZV can reactivate to cause herpes zoster (shingles), a debilitating disease that affects one million individuals in the US alone annually. Current vaccines against varicella (Varivax) and herpes zoster (Zostavax) are not 100% efficacious. Specifically, studies have shown that 1 dose of varivax can lead to breakthrough varicella, alb ... | 2011 | 22102814 |
| simian varicella virus is present in macrophages, dendritic cells, and t cells in lymph nodes of rhesus macaques after experimental reactivation. | like varicella-zoster virus (vzv), simian varicella virus (svv) reactivates to produce zoster. in the present study, 5 rhesus macaques were inoculated intrabronchially with svv, and 5 months later, 4 monkeys were immunosuppressed; 1 monkey was not immunosuppressed but was subjected to the stress of transportation. in 4 monkeys, a zoster rash developed 7 to 12 weeks after immunosuppression, and a rash also developed in the monkey that was not immunosuppressed. analysis at 24 to 48 h after zoster ... | 2015 | 26178993 |
| the orf61 protein encoded by simian varicella virus and varicella-zoster virus inhibits nf-κb signaling by interfering with iκbα degradation. | varicella-zoster virus (vzv) causes chickenpox upon primary infection and establishes latency in ganglia. reactivation from latency causes herpes zoster, which may be complicated by postherpetic neuralgia. innate immunity mediated by interferon and proinflammatory cytokines represents the first line of immune defense upon infection and reactivation. vzv is known to interfere with multiple innate immune signaling pathways, including the central transcription factor nf-κb. however, the role of the ... | 2015 | 26085158 |
| varicella virus-host interactions during latency and reactivation: lessons from simian varicella virus. | varicella zoster virus (vzv) is a neurotropic alphaherpesvirus and the causative agent of varicella (chickenpox) in humans. following primary infection, vzv establishes latency in the sensory ganglia and can reactivate to cause herpes zoster, more commonly known as shingles, which causes significant morbidity, and on rare occasions mortality, in the elderly. because vzv infection is highly restricted to humans, the development of a reliable animal model has been challenging, and our understandin ... | 2018 | 30619226 |
| simian varicella virus causes robust transcriptional changes in t cells that support viral replication. | varicella zoster virus (vzv) causes varicella (chickenpox) during acute infection. several studies have shown that t cells are early and preferential targets of vzv infection that play a critical role in disseminating vzv in to the skin and ganglia. however, the transcriptional changes that occur in vzv-infected t cells remain unclear due to limited access to clinical samples and robust translational animal models. in this study, we used a nonhuman primate model of vzv infection where rhesus mac ... | 2017 | 28698046 |
| current in vivo models of varicella-zoster virus neurotropism. | varicella-zoster virus (vzv), an exclusively human herpesvirus, causes chickenpox and establishes a latent infection in ganglia, reactivating decades later to produce zoster and associated neurological complications. an understanding of vzv neurotropism in humans has long been hampered by the lack of an adequate animal model. for example, experimental inoculation of vzv in small animals including guinea pigs and cotton rats results in the infection of ganglia but not a rash. the severe combined ... | 2019 | 31159224 |
| elevated serum substance p during simian varicella virus infection in rhesus macaques: implications for chronic inflammation and adverse cerebrovascular events. | varicella and zoster, produced by varicella-zoster virus (vzv), are associated with an increased risk of stroke that may be due to persistent inflammation and hypercoagulability. because substance p is associated with inflammation, hypercoagulability, and atherosclerotic plaque rupture that may contribute to increased stroke risk after vzv infection, we measured serum substance p in simian varicella virus-infected rhesus macaques. we found significantly increased and persistent serum substance p ... | 2020 | 32964407 |
| simian varicella virus dna in saliva and buccal cells after experimental acute infection in rhesus macaques. | simian varicella virus (svv) infection of non-human primates is the counterpart of varicella zoster virus (vzv) infection in humans. to develop non-invasive methods of assessing svv infection, we tested for the presence of svv dna in saliva, as has been documented in human vzv infection, and in buccal cells to determine whether epithelial cells might provide a more reliable source of material for analysis. five rhesus macaques intratracheally inoculated with svv all developed varicella with vire ... | 2019 | 31143167 |
| attenuation of simian varicella virus infection by enhanced green fluorescent protein in rhesus macaques. | simian varicella virus (svv), the primate counterpart of varicella zoster virus, causes varicella (chickenpox), establishes latency in ganglia and reactivates to produce zoster. we previously demonstrated that a recombinant svv expressing the enhanced green fluorescent protein (rsvv.egfp) is slightly attenuated both in culture and infected monkeys. herein, we generated two additional recombinant svvs to visualize infected cells in vitro and in vivo one harbors egfp fused to the n-terminus of ope ... | 2018 | 29343566 |