| use of herpesvirus saimiri-immortalized macaque cd4(+) t cell clones as stimulators and targets for assessment of ctl responses in macaque/aids models. | herpesvirus saimiri (hvs), a nonhuman primate gamma herpes virus, was used to immortalize pig-tailed macaque cd4(+) t lymphocytes. the hvs-immortalized t cell lines were used to develop cd4(+) t cell clones from two animals. three cd4(+) t cell clones were further characterized for the expression of cell surface markers. all expressed cd2, cd4, cd58, cd69 and cd80 and therefore resembled activated t cells. these clones required exogenous il-2 for efficient growth and were found to be highly susc ... | 1999 | 10594353 |
| molecular evolution of human immunodeficiency virus env in humans and monkeys: similar patterns occur during natural disease progression or rapid virus passage. | neonatal rhesus macaque 95-3 was inoculated with nonpassaged simian-human immunodeficiency virus strain shiv-vpu(+), which encodes env of the laboratory-adapted human immunodeficiency virus (hiv) strain iiib and is considered nonpathogenic. cd4(+) t-cell counts dropped to <200 cells/microl within 4.6 years, and monkey 95-3 died with opportunistic infections 5.9 years postinoculation. transfer of blood from 95-3 to two naive adult macaques resulted in high peak viral loads and rapid, persistent t ... | 2002 | 11967343 |
| simian-human immunodeficiency virus-associated nephropathy in macaques. | a number of chimeric simian-human immunodeficiency virus (shiv) viruses containing tat, rev, vpu, and env from hiv-1 (strain hxbc2) in a genetic background of simian immunodeficiency virus (siv(mac)239) have been derived from the parental nonpathogenic shiv-4 virus. in this article we examine the renal pathology associated with the derivation of these pathogenic shiv strains. the first of the pathogenic shivs, shiv(ku-1), is associated with rapid cd4(+) t cell loss and opportunistic infections a ... | 2000 | 10957726 |
| a molecular clone of simian-human immunodeficiency virus (deltavpushiv(ku-1bmc33)) with a truncated, non-membrane-bound vpu results in rapid cd4(+) t cell loss and neuro-aids in pig-tailed macaques. | we report on the role of vpu in the pathogenesis of a molecularly cloned simian-human immunodeficiency virus (shiv(ku-1bmc33)), in which the tat, rev, vpu, env, and nef genes derived from the uncloned shiv(ku-1b) virus were inserted into the genetic background of parental nonpathogenic shiv-4. a mutant was constructed (deltavpushiv(ku-1bmc33)) in which 42 of 82 amino acids of vpu were deleted. phase partitioning studies revealed that the truncated vpu was not an integral membrane protein, and pu ... | 2000 | 10873754 |
| enhanced infectivity of an r5-tropic simian/human immunodeficiency virus carrying human immunodeficiency virus type 1 subtype c envelope after serial passages in pig-tailed macaques (macaca nemestrina). | the increasing prevalence of human immunodeficiency virus type 1 (hiv-1) subtype c infection worldwide calls for efforts to develop a relevant animal model for evaluating strategies against the transmission of the virus. a chimeric simian/human immunodeficiency virus (shiv), shiv(chn19), was generated with a primary, non-syncytium-inducing hiv-1 subtype c envelope from a chinese strain in the background of shiv(33). unlike r5-tropic shiv(162), shiv(chn19) was not found to replicate in rhesus cd4 ... | 2000 | 10864663 |
| induction of autoantibodies to ccr5 in macaques and subsequent effects upon challenge with an r5-tropic simian/human immunodeficiency virus. | antibodies against ccr5, the major coreceptor for human immunodeficiency virus type 1 (hiv-1), may have antiviral potential as viral fusion inhibitors. in this study, we generated a virus-like particle (vlp)-based vaccine that effectively breaks b-cell tolerance and elicits autoantibodies against ccr5 in pig-tailed macaques. initial studies in mice identified a polypeptide comprising the n-terminal domain of pig-tailed macaque ccr5 fused to streptavidin that, when conjugated at high density to b ... | 2004 | 15047820 |
| emergence of a highly pathogenic simian/human immunodeficiency virus in a rhesus macaque treated with anti-cd8 mab during a primary infection with a nonpathogenic virus. | although simian/human immunodeficiency virus (shiv) strain dh12 replicates to high titers and causes immunodeficiency in pig-tailed macaques, virus loads measured in shiv(dh12)-infected rhesus monkeys are consistently 100-fold lower and none of 22 inoculated animals have developed disease. we previously reported that the administration of anti-human cd8 mab to rhesus macaques at the time of primary shiv(dh12) infection resulted in marked elevations of virus loads. one of the treated animals expe ... | 1999 | 10570196 |
| characterization of a neutralization-escape variant of shivku-1, a virus that causes acquired immune deficiency syndrome in pig-tailed macaques. | a chimeric simian-human immunodeficiency virus (shiv-4) containing the tat, rev, vpu, and env genes of hiv type 1 (hiv-1) in a genetic background of sivmac239 was used to develop an animal model in which a primate lentivirus expressing the hiv-1 envelope glycoprotein caused acquired immune deficiency syndrome (aids) in macaques. an shiv-infected pig-tailed macaque that died from aids at 24 weeks postinoculation experienced two waves of viremia: one extending from weeks 2-8 and the second extendi ... | 1999 | 10087226 |
| passively administered neutralizing serum that protected macaques against infection with parenterally inoculated pathogenic simian-human immunodeficiency virus failed to protect against mucosally inoculated virus. | macaques inoculated orally, vaginally, or parenterally with shiv(ku-1) develop severe systemic infection, acute loss of cd4+ t cells, and aids. we showed in a previous report that passive immunization with neutralizing serum protected macaques against infection with parenterally inoculated pathogenic shiv given 24 hr later. in the study reported here we asked whether the identical passive immunization protocol would protect macaques against infection with pathogenic shiv following oral inoculati ... | 1999 | 10082123 |
| neutralizing antibody directed against the hiv-1 envelope glycoprotein can completely block hiv-1/siv chimeric virus infections of macaque monkeys. | virus-specific antibodies protect individuals against a wide variety of viral infections. to assess whether human immunodeficiency virus type 1 (hiv-1) envelope-specific antibodies confer resistance against primate lentivirus infections, we purified immunoglobulin (igg) from chimpanzees infected with several different hiv-1 isolates, and used this for passive immunization of pig-tailed macaques. these monkeys were subsequently challenged intravenously with a chimeric simian-human immunodeficienc ... | 1999 | 9930869 |
| chronology of genetic changes in the vpu, env, and nef genes of chimeric simian-human immunodeficiency virus (strain hxb2) during acquisition of virulence for pig-tailed macaques. | recently, we developed a highly pathogenic variant of simian-human immunodeficiency virus, shiv-4 (containing the tat, rev, vpu, and env of the hxb2 strain of hiv-1 in a genetic background of sivmac239), through a series of four bone marrow-bone marrow passages-first in rhesus monkeys and then in pig-tailed macaques [joag et al. (1996) j. virol. 70, 3189-3197]. inoculation of pig-tailed macaques with this pathogenic virus (shivku-1) causes subtotal elimination of cd4(+) t cells and fatal opportu ... | 1998 | 9721236 |
| simian-human immunodeficiency virus (shiv) containing the nef/long terminal repeat region of the highly virulent sivsmmpbj14 causes pbj-like activation of cultured resting peripheral blood mononuclear cells, but the chimera showed no increase in virulence. | sivsmmpbj14 is a highly pathogenic lentivirus which causes acute diarrhea, rash, massive lymphocyte proliferation predominantly in the gastrointestinal tract, and death within 7 to 14 days. in cell culture, the virus has mitogenic effects on resting macaque t lymphocytes. in contrast, sivmac239 causes aids in rhesus macaques, generally within 2 years after inoculation. in a previous study, replacement of amino acid residues 17 and 18 of the nef protein of sivmac239 with the corresponding amino a ... | 1998 | 9573293 |
| neuropathogenesis of chimeric simian/human immunodeficiency virus infection in pig-tailed and rhesus macaques. | we recently reported that a chimeric simian/human immunodeficiency virus (shivku-1) developed in our laboratory caused progressive depletion of cd4+ t lymphocytes and aids within 6 months of inoculation into pig-tailed macaques (m. nemestrina). none of the pig-tailed macaques showed productive shiv infection in the central nervous system (cns). in this report, we show that by further passage of the pathogenic virus in rhesus macaques [m. mulatta], we have derived a new strain of shiv (shivku-2) ... | 1997 | 9217970 |
| a cell-free stock of simian-human immunodeficiency virus that causes aids in pig-tailed macaques has a limited number of amino acid substitutions in both sivmac and hiv-1 regions of the genome and has offered cytotropism. | we have examined both the sequence changes in the ltr, gag, vif, vpr, vpx, tat, rev, vpu, env, and nef genes and the cell tropism of a cell-free stock of chimeric simian-human immunodeficiency virus (shiv) isolated from the cerebrospinal fluid of a pig-tailed macaque (pnb) that developed aids. this virus (shivku-1) is highly pathogenic when inoculated into other macaques. dna sequence analysis of pcr-amplified products revealed a total of 5 nucleotide changes in the ltr while vif had 2 consensus ... | 1997 | 9168893 |
| characterization of the pathogenic ku-shiv model of acquired immunodeficiency syndrome in macaques. | by animal-to-animal passage in macaques we derived a pathogenic chimeric simian-human immunodeficiency virus (shiv) that caused cd4+ t cell loss and aids in pigtail macaques and used it to inoculate 20 rhesus and pigtail macaques by the intravaginal and intravenous routes. on the basis of the outcome of infection and patterns of cd4+ t cell loss and viral load, disease was classified into four patterns: acute, subacute, chronic, and nonprogressive infection. during the study period, 15 of the 20 ... | 1997 | 9168232 |
| animal model of mucosally transmitted human immunodeficiency virus type 1 disease: intravaginal and oral deposition of simian/human immunodeficiency virus in macaques results in systemic infection, elimination of cd4+ t cells, and aids. | chimeric simian/human immunodeficiency virus (shiv) consists of the env, vpu, tat, and rev genes of human immunodeficiency virus type 1 (hiv-1) on a background of simian immunodeficiency virus (siv). we derived a shiv that caused cd4+ cell loss and aids in pig-tailed macaques (s. v. joag, z. li, l. foresman, e. b. stephens, l. j. zhao, i. adany, d. m. pinson, h. m. mcclure, and o. narayan, j. virol. 70:3189-3197, 1996) and used a cell-free stock of this virus (shiv(ku-1)) to inoculate macaques b ... | 1997 | 9094679 |
| chimeric simian/human immunodeficiency virus that causes progressive loss of cd4+ t cells and aids in pig-tailed macaques. | by animal-to-animal passage of simian/human immunodeficiency virus (shiv) in pig-tailed macaques, we have developed a macaque model of human immunodeficiency virus type 1 (hiv-1) disease in humans. passaging was begun with a chimeric virus containing the env gene of hiv-1 hxbc2 and the gag and pol genes of simian immunodeficiency virus sivmac239. shiv was passaged serially in cohorts of two macaques each, using bone marrow-to-bone marrow transfers at 5, 5, and 16 weeks for passages 2, 3, and 4, ... | 1996 | 8627799 |
| siv of stump-tailed macaque (sivstm) is a divergent asian isolate. | analysis of molecularly cloned dnas of sivs isolated from asian rhesus macaque (macaca mulatta; sivmac) and pig-tailed macaque (macaca nemestrina; sivmne) has indicated a high degree of sequence homology between these viruses. thus sivmac and sivmne might have originated from the same or very closely related viruses. we have cloned and sequenced a pcr-amplified segment containing the ltr sequences of siv originating from a stump-tailed macaque (macaca arctoides; sivstm). comparative sequence ana ... | 1991 | 1719204 |
| comparative efficacy of subtype ae simian-human immunodeficiency virus priming and boosting vaccines in pigtail macaques. | vaccination against aids is hampered by great diversity between human immunodeficiency virus (hiv) strains. heterologous b-subtype-based simian-human immunodeficiency virus (shiv) dna prime and poxvirus boost vaccine regimens can induce partial, t-cell-mediated, protective immunity in macaques. we analyzed a set of dna, recombinant fowlpox viruses (fpv), and vaccinia viruses (vv) expressing subtype ae hiv type 1 (hiv-1) tat, rev, and env proteins and siv gag/pol in 30 pigtail macaques. siv gag-s ... | 2007 | 17050602 |
| infection of macaques with an r5-tropic shiv bearing a chimeric envelope carrying subtype e v3 loop among subtype b framework. | to establish simian/human immunodeficiency virus (shiv) clones bearing a chimeric envelope carrying subtype e v3 loop among subtype b envelope, four subtype e v3 sequences were substituted into shiv(md14), a shiv clone bearing an envelope derived from a cxcr4 (x4)/ccr5 (r5)-dual tropic subtype b hiv-1 strain. shiv-th09v3, an only v3-chimera clone capable of replicating in human and macaque peripheral blood mononuclear cells (pbmcs), was propagated in pig-tailed macaque pbmcs and in cynomolgus ma ... | 2003 | 12721803 |
| cd4+ lymphocytopenia in acute infection of asian macaques by a vaginally transmissible subtype-c, ccr5-tropic simian/human immunodeficiency virus (shiv). | an r5-tropic shiv(chn19p4) was previously generated using a primary hiv-1 subtype-c envelope. we have further characterized this shiv in two species of macaques. to determine whether this isolate is transmissible vaginally, female pig-tailed macaques were inoculated with 2 x 10(3) tcid50 of shiv(chn19p4) by the vaginal route. animals became infected with a high peak plasma viremia (>10(7) viral copies/ml) and rapid seroconversion. the viremia was accompanied by cd4+ lymphocytopenia in the gut la ... | 2002 | 12045675 |
| pathogenic and nef-interrupted simian-human immunodeficiency viruses traffic to the macaque cns and cause astrocytosis early after inoculation. | several studies have shown that deletion of the nef gene of simian immunodeficiency virus (siv) and simian-human immunodeficiency virus (shiv) results in attenuated viruses. however, studies have not critically examined trafficking of attenuated viruses to the central nervous system (cns) at early stages after inoculation. in this study, we investigated the colocalization of pathogenic and vpu-negative, nef-interrupted shivs at early stages following inoculation. the first virus, designated shiv ... | 2002 | 12036316 |
| innate differences between simian-human immunodeficiency virus (shiv)(ku-2)-infected rhesus and pig-tailed macaques in development of neurological disease. | neurological disease associated with hiv infection results from either primary replication of the virus or a combination of virus infection and replication of opportunistic pathogens in the cns. recent studies indicate that the primary infection is mediated mainly by viruses that utilize ccr5 as the coreceptor; it is not known whether the syndrome can be mediated by viruses that use the cxcr4 coreceptor. the macaque model of the disease using simian immunodeficiency virus (siv) has confirmed tha ... | 2002 | 12033765 |
| deletion of the vpu sequences prior to the env in a simian-human immunodeficiency virus results in enhanced env precursor synthesis but is less pathogenic for pig-tailed macaques. | the vpu protein of human immunodeficiency virus type 1 (hiv-1) has been reported to enhance virion release from infected cells and to down-regulate the expression of cd4 on infected cells. previous studies have shown that vpu and the envelope glycoprotein precursor (gp160) are translated from different reading frames of the same bicistronic messenger rna (mrna). in order to assess the effect of the vpu sequences 5' to the env open reading frame on env biosynthesis and pathogenesis, we have const ... | 2002 | 11886245 |
| determination of a statistically valid neutralization titer in plasma that confers protection against simian-human immunodeficiency virus challenge following passive transfer of high-titered neutralizing antibodies. | we previously reported that high-titered neutralizing antibodies directed against the human immunodeficiency virus type 1 (hiv-1) envelope can block the establishment of a simian immunodeficiency virus (siv)/hiv chimeric virus (shiv) infection in two monkeys following passive transfer (r. shibata et al., nat. med. 5:204-210, 1999). in the present study, increasing amounts of neutralizing immunoglobulin g (igg) were administered to 15 pig-tailed macaques in order to obtain a statistically valid p ... | 2002 | 11836389 |
| infectious simian/human immunodeficiency virus with human immunodeficiency virus type 1 subtype c from an african isolate: rhesus macaque model. | human immunodeficiency virus type 1 (hiv-1) subtype c is responsible for more than 56% of all infections in the hiv and aids pandemic. it is the predominant subtype in the rapidly expanding epidemic in southern africa. to develop a relevant model that would facilitate studies of transmission, pathogenesis, and vaccine development for this subtype, we generated shiv(mj4), a simian/human immunodeficiency virus (shiv) chimera based on hiv-1 subtype c. shiv(mj4) contains the majority of env, the ent ... | 2001 | 11689623 |
| evidence for early local viral replication and local production of antiviral immunity upon mucosal simian-human immunodeficiency virus shiv(89.6) infection in macaca nemestrina. | transmission of human immunodeficiency virus type 1 (hiv-1) is largely a result of heterosexual exposure, leading many investigators to evaluate mucosal vaccines for protection against intravaginal (i.vag.) transmission in macaque models of aids. relatively little is known, however, about the dynamics of viral replication and the ensuing immune response following mucosal infection. we have utilized a simian-human immunodeficiency virus (shiv) to study the differences in viremia, cd4 t-cell perce ... | 2001 | 11507204 |
| the presence of the casein kinase ii phosphorylation sites of vpu enhances the cd4(+) t cell loss caused by the simian-human immunodeficiency virus shiv(ku-lbmc33) in pig-tailed macaques. | the simian-human immunodeficiency virus (shiv)/ macaque model for human immunodeficiency virus type 1 has become a useful tool to assess the role of vpu in lentivirus pathogenesis. in this report, we have mutated the two phosphorylated serine residues of the hiv-1 vpu to glycine residues and have reconstructed a shiv expressing this nonphosphorylated vpu (shiv(s52,56g)). expression studies revealed that this protein was localized to the same intracellular compartment as wild-type vpu. to determi ... | 2003 | 12954211 |
| multigene dna priming-boosting vaccines protect macaques from acute cd4+-t-cell depletion after simian-human immunodeficiency virus shiv89.6p mucosal challenge. | we evaluated four priming-boosting vaccine regimens for the highly pathogenic simian human immunodeficiency virus shiv89.6p in macaca nemestrina. each regimen included gene gun delivery of a dna vaccine expressing all shiv89.6 genes plus env gp160 of shiv89.6p. additional components were two recombinant vaccinia viruses, expressing shiv89.6 gag-pol or env gp160, and inactivated shiv89.6 virus. we compared (i) dna priming/dna boosting, (ii) dna priming/inactivated virus boosting, (iii) dna primin ... | 2003 | 14557642 |
| fusion of the upstream vpu sequences to the env of simian human immunodeficiency virus (shiv(ku-1bmc33)) results in the synthesis of two envelope precursor proteins, increased numbers of virus particles associated with the cell surface and is pathogenic for pig-tailed macaques. | previous studies have shown that the gene coding for the vpu protein of the human immunodeficiency virus type 1 (hiv-1) is 5' to the env gene, is in a different reading frame, and overlaps the env by 90 nucleotides. in this study, we examined the processing of the env protein as well as the maturation and infectivity of a virus (shiv(vpenv)) in which a single nucleotide was removed at the vpu-env junction, fusing the first 162 bases of vpu to the env orf. pulse-chase analysis revealed that shiv( ... | 2004 | 15165822 |
| efficacy of dna and fowlpox virus priming/boosting vaccines for simian/human immunodeficiency virus. | further advances are required in understanding protection from aids by t-cell immunity. we analyzed a set of multigenic simian/human immunodeficiency virus (shiv) dna and fowlpox virus priming and boosting vaccines for immunogenicity and protective efficacy in outbred pigtail macaques. the number of vaccinations required, the effect of dna vaccination alone, and the effect of cytokine (gamma interferon) coexpression by the fowlpox virus boost was also studied. a coordinated induction of high lev ... | 2004 | 15564490 |
| multiple vaginal exposures to low doses of r5 simian-human immunodeficiency virus: strategy to study hiv preclinical interventions in nonhuman primates. | a nonhuman-primate model of human immunodeficiency virus type 1 (hiv-1) infection that more closely emulates human heterosexual transmission by use of multiple exposures to low doses of virus is critical to better evaluate intervention strategies that include microbicides or vaccines. in this report, we describe such a system that uses female pig-tailed macaques exposed vaginally to a ccr5-using simian-human immunodeficiency virus (shiv(sf162p3)) at weekly intervals. results of dose-titration ex ... | 2004 | 15609225 |
| rapid viral escape at an immunodominant simian-human immunodeficiency virus cytotoxic t-lymphocyte epitope exacts a dramatic fitness cost. | escape from specific t-cell responses contributes to the progression of human immunodeficiency virus type 1 (hiv-1) infection. t-cell escape viral variants are retained following hiv-1 transmission between major histocompatibility complex (mhc)-matched individuals. however, reversion to wild type can occur following transmission to mhc-mismatched hosts in the absence of cytotoxic t-lymphocyte (ctl) pressure, due to the reduced fitness of the escape mutant virus. we estimated both the strength of ... | 2005 | 15827187 |
| phenotypic and kinetic analysis of effective simian-human immunodeficiency virus-specific t cell responses in dna--and fowlpox virus-vaccinated macaques. | although t cell immunity is important in the control of hiv-1 infection, the characteristics of effective hiv-specific t cell responses are unclear. we previously observed protection from virulent shiv challenges in macaques administered priming with dna vaccines and boosting with recombinant fowlpox viruses expressing shared siv gag antigens. we therefore performed a detailed kinetic and phenotypic study of the t cell immunity induced by these vaccines prior to and following shiv challenge util ... | 2005 | 15907968 |
| scrambling of the amino acids within the transmembrane domain of vpu results in a simian-human immunodeficiency virus (shivtm) that is less pathogenic for pig-tailed macaques. | previous studies have shown that the transmembrane (tm) domain of the subtype b vpu enhances virion release from cells and some studies have shown that this domain may form an oligomeric structure with properties of an ion channel. to date, no studies have been performed to assess the role of this domain in virus pathogenesis in a macaque model of disease. using a pathogenic molecular clone of simian human immunodeficiency virus (shivku-1bmc33), we have generated a novel virus in which the trans ... | 2005 | 15975620 |
| the pigtail macaque mhc class i allele mane-a*10 presents an immundominant siv gag epitope: identification, tetramer development and implications of immune escape and reversion. | the pigtail macaque (macaca nemestrina) is a common model for the study of aids. the pigtail major histocompatibility complex class i allele mane-a*10 restricts an immunodominant simian immunodeficiency virus (siv) gag epitope (kp9) which rapidly mutates to escape t cell recognition following acute simian/human immunodeficiency virus infection. two technologies for the detection of mane-a*10 in outbred pigtail macaques were developed: reference strand-mediated conformational analysis and sequenc ... | 2005 | 16128923 |
| substitution of the transmembrane domain of vpu in simian-human immunodeficiency virus (shivku1bmc33) with that of m2 of influenza a results in a virus that is sensitive to inhibitors of the m2 ion channel and is pathogenic for pig-tailed macaques. | the vpu protein of human immunodeficiency virus type 1 has been shown to shunt the cd4 receptor molecule to the proteasome for degradation and to enhance virus release from infected cells. the exact mechanism by which the vpu protein enhances virus release is currently unknown but some investigators have shown that this function is associated with the transmembrane domain and potential ion channel properties. in this study, we determined if the transmembrane domain of vpu could be functionally s ... | 2006 | 16199074 |
| consistent patterns of change during the divergence of human immunodeficiency virus type 1 envelope from that of the inoculated virus in simian/human immunodeficiency virus-infected macaques. | we have analyzed changes to proviral env gp120 sequences and the development of neutralizing antibodies (nabs) during 1 year of simian/human immunodeficiency virus shiv-89.6p infection in 11 macaca nemestrina macaques. seven macaques had significant env divergence from that of the inoculum, and macaques with greater divergence had higher titers of homologous nabs. substitutions in sequons encoding potential n-linked glycosylation sites (pngs) were among the first to be established, although over ... | 2006 | 16379001 |
| short communication: characteristics of effective immune control of simian/human immunodeficiency virus in pigtail macaques. | considerable evidence suggests both hiv-specific t cells and neutralizing antibodies (nab) can, separately, assist control of viremia. t cell and nab responses were studied in detail in three pigtail macaques protected from chronic simian/human immunodeficiency virus (shiv) viremia by dna prime/fowlpoxvirus boost vaccine regimens. immunity was studied both after an initial intrarectal shiv challenge, as well as during cd8 t cell depletion and a subsequent intravenous shiv rechallenge. remarkably ... | 2006 | 16438642 |
| a single amino acid substitution within the transmembrane domain of the human immunodeficiency virus type 1 vpu protein renders simian-human immunodeficiency virus (shiv(ku-1bmc33)) susceptible to rimantadine. | previous studies from our laboratory have shown that the transmembrane domain (tm) of the vpu protein of human immunodeficiency virus type 1 (hiv-1) contributes to the pathogenesis of shiv(ku-1bmc33) in macaques and that the tm domain of vpu could be replaced with the m2 protein viroporin from influenza a virus. recently, we showed that the replacement of the tm domain of vpu with that of the m2 protein of influenza a virus resulted in a virus (shiv(m2)) that was sensitive to rimantadine [hout, ... | 2006 | 16458946 |
| evidence for persistent, occult infection in neonatal macaques following perinatal transmission of simian-human immunodeficiency virus sf162p3. | to model human immunodeficiency virus (hiv) perinatal transmission, we studied infection of simian-human immunodeficiency virus (shiv) sf162p3 in 10 pregnant macaca nemestrina females and their offspring. four of nine infants born to and suckled by these dams had evidence of infection, a transmission rate of 44.4% (95% confidence interval, 13.7% to 78.8%). we quantified transplacentally acquired and de novo env-specific immunoglobulin g (igg), igm, and neutralizing antibodies in newborns. transm ... | 2007 | 17079310 |
| early dysregulation of cripto-1 and immunomodulatory genes in the cerebral cortex in a macaque model of neuroaids. | human immunodeficiency virus type 1 (hiv-1) and related primate lentiviruses are known to enter the central nervous system (cns) during the primary phase of infection. neuroinvasion by simian immunodeficiency virus and simian human immunodeficiency virus (shiv) is characterized by transient meningitis and astrocytosis. in this report, we used targeted cytokine cdna arrays to analyze cortical brain tissue from four pig-tailed macaques inoculated for 2 weeks with pathogenic shiv(50olnv) and a norm ... | 2006 | 17084529 |
| utility of human immunodeficiency virus type 1 envelope as a t-cell immunogen. | human immunodeficiency virus (hiv)-specific cd8 t lymphocytes are important for the control of viremia, but the relative utility of responses to the various hiv proteins is controversial. immune responses that force escape mutations that exact a significant fitness cost from the mutating virus would help slow progression to aids. the hiv envelope (env) protein is subject to both humoral and cellular immune responses, suggesting that multiple rounds of mutation are needed to facilitate viral esca ... | 2007 | 17898063 |
| modulation of the severe cd4+ t-cell loss caused by a pathogenic simian-human immunodeficiency virus by replacement of the subtype b vpu with the vpu from a subtype c hiv-1 clinical isolate. | previously, we showed that the vpu protein from subtype c human immunodeficiency virus type 1 (hiv-1) was efficiently targeted to the cell surface, suggesting that this protein has biological properties that differ from the well-studied subtype b vpu protein. in this study, we have further analyzed the biological properties of the subtype c vpu protein. flow cytometric analysis revealed that the subtype b vpu (strain hxb2) was more efficient at down-regulating cd4 surface expression than the vpu ... | 2008 | 17950774 |
| limited maintenance of vaccine-induced simian immunodeficiency virus-specific cd8 t-cell receptor clonotypes after virus challenge. | t-cell receptors (tcrs) govern the specificity, efficacy, and cross-reactivity of cd8 t cells. here, we studied cd8 t-cell clonotypes from mane-a*10(+) pigtail macaques responding to the simian immunodeficiency virus (siv) gag kp9 epitope in a setting of vaccination and subsequent viral challenge. we observed a diverse tcr repertoire after dna, recombinant poxvirus, and live attenuated virus vaccination, with none of 59 vaccine-induced kp9-specific tcrs being identical between macaques. the kp9- ... | 2008 | 18508897 |
| pathogenic infection of macaca nemestrina with a ccr5-tropic subtype-c simian-human immunodeficiency virus. | although pig-tailed macaques (macaca nemestrina) have been used in aids research for years, less is known about the early immunopathogenic events in this species, as compared to rhesus macaques (macaca mulatta). similarly, the events in early infection are well-characterized for simian immunodeficiency viruses (siv), but less so for chimeric simian-human immunodeficiency viruses (shiv), although the latter have been widely used in hiv vaccine studies. here, we report the consequences of intrarec ... | 2009 | 19602283 |
| does cytolysis by cd8+ t cells drive immune escape in hiv infection? | cd8(+) "cytotoxic" t cells are important for the immune control of hiv and the closely related simian models siv and chimeric simian-human immunodeficiency virus (shiv), although the mechanisms of this control are unclear. one effect of cd8(+) t cell-mediated recognition of virus-infected cells is the rapid selection of escape mutant (em) virus that is not recognized. to investigate the mechanisms of virus-specific cd8(+) t cell control during immune escape in vivo, we used a real-time pcr assay ... | 2010 | 20881189 |
| genetic diversity of simian immunodeficiency virus encoding hiv-1 reverse transcriptase persists in macaques despite antiretroviral therapy. | the impact of antiretroviral therapy (art) on the genetics of simian immunodeficiency virus (siv) or human immunodeficiency virus (hiv) populations has been incompletely characterized. we analyzed siv genetic variation before, during, and after art in a macaque model. six pigtail macaques were infected with an siv/hiv chimeric virus, rt-shiv(mne), in which siv reverse transcriptase (rt) was replaced by hiv-1 rt. three animals received a short course of efavirenz (efv) monotherapy before combinat ... | 2010 | 21084490 |
| adaptation of subtype a human immunodeficiency virus type 1 envelope to pig-tailed macaque cells. | the relevance of simian/human immunodeficiency virus (shiv) infection of macaques to hiv-1 infection in humans depends on how closely shivs mimic hiv-1 transmission, pathogenesis, and diversity. circulating hiv-1 strains are predominantly subtypes c and a and overwhelmingly require ccr5 for entry, yet most shivs incorporate cxcr4-using subtype b envelopes (envs). while pathogenic subtype c-based shivs have been constructed, the subtype a-based shivs (shiv-as) constructed to date have been unable ... | 2011 | 21325401 |
| increased susceptibility to vaginal simian/human immunodeficiency virus transmission in pig-tailed macaques coinfected with chlamydia trachomatis and trichomonas vaginalis. | sexually transmitted infections (stis) are associated with an increased risk of human immunodeficiency virus (hiv) infection, but their biological effect on hiv susceptibility is not fully understood. | 2014 | 24755433 |
| combination emtricitabine and tenofovir disoproxil fumarate prevents vaginal simian/human immunodeficiency virus infection in macaques harboring chlamydia trachomatis and trichomonas vaginalis. | genital inflammation associated with sexually transmitted infections increases susceptibility to human immunodeficiency virus (hiv), but it is unclear whether the increased risk can reduce the efficacy of pre-exposure prophylaxis (prep). we investigated whether coinfection of macaques with chlamydia trachomatis and trichomonas vaginalis decreases the prophylactic efficacy of oral emtricitabine (ftc)/tenofovir disoproxil fumarate (tdf). macaques were exposed to simian/human immunodeficiency virus ... | 2016 | 26743846 |
| a depot medroxyprogesterone acetate dose that models human use and its effect on vaginal shiv acquisition risk. | hormonal contraception with depot medroxyprogesterone acetate (dmpa) may increase hiv acquisition risk, but observational human studies are inconclusive, and animal models can help investigate this risk. in this study, we test the impact of a low dmpa dose, designed to resemble human contraceptive use, on simian-human immunodeficiency virus (shiv) acquisition risk in pigtail macaques (macaca nemestrina). | 2016 | 27355414 |
| cataloguing of potential hiv susceptibility factors during the menstrual cycle of pig-tailed macaques by using a systems biology approach. | our earlier studies with pig-tailed macaques demonstrated various simian-human immunodeficiency virus (shiv) susceptibilities during the menstrual cycle, likely caused by cyclic variations in immune responses in the female genital tract. there is concern that high-dose, long-lasting, injectable progestin-based contraception could mimic the high-progesterone luteal phase and predispose women to human immunodeficiency type 1 (hiv-1) acquisition and transmission. in this study, we adopted a systems ... | 2015 | 26109722 |
| a comparison of lower genital tract glycogen and lactic acid levels in women and macaques: implications for hiv and siv susceptibility. | understanding factors that affect heterosexual transmission of hiv in women is of great importance. lactobacilli in the lower genital tract of women utilize glycogen in vaginal epithelial cells as an energy source and produce lactic acid. the resultant vaginal acidity is believed to provide protection against hiv infection. conversely, bacterial vaginosis (bv) is characterized by less lactic acid, a higher ph, and is associated with increased susceptibility to hiv infection. because vaginal infe ... | 2011 | 21595610 |
| massive occlusive thrombosis of the pulmonary artery in pigtailed macaques chronically infected with r5-tropic simian-human immunodeficiency virus. | pulmonary arterial hypertension (pah) has been identified as a serious complication of hiv infection. | 2015 | 25174584 |
| shiv susceptibility changes during the menstrual cycle of pigtail macaques. | hormonal changes during menstrual cycling may affect susceptibility to hiv. | 2014 | 24779484 |
| comparison of the vaginal environment of macaca mulatta and macaca nemestrina throughout the menstrual cycle. | pigtail macaques, macaca nemestrina (pt), are more susceptible to vaginal transmission of simian immunodeficiency virus (siv) and other sexually transmitted diseases (std) than rhesus macaques (rm). however, comparative studies to explore the reasons for these differences are lacking. | 2014 | 24521395 |
| evaluation of pigtail macaques as a model for the effects of copper intrauterine devices on hiv infection. | long-acting, hormonal contraception may increase hiv risk. copper intrauterine devices (iuds) could serve as non-hormonal alternatives. we pilot a pigtail macaque model for evaluating hiv susceptibility factors during copper iud use. | 2014 | 24372425 |
| repetitive exposures with simian/human immunodeficiency viruses: strategy to study hiv pre-clinical interventions in non-human primates. | non-human primate models for human immunodeficiency virus (hiv) infection represent a valuable pre-clinical tool to evaluate interventions (e.g., topical microbicides, vaccines, and chemoprophylaxis) designed to prevent transmission or slow disease progression after infection. standard transmission models use a single-dose exposure with high, non-physiologic levels of virus to approach 100% infection rates of control animals. these single-exposure models do not represent the circumstances of muc ... | 2006 | 16872284 |
| generation of hiv-1 derivatives that productively infect macaque monkey lymphoid cells. | the narrow host range of human immunodeficiency virus type 1 (hiv-1) is caused in part by innate cellular factors such as apolipoprotein b mrna-editing enzyme-catalytic polypeptide-like 3g (apobec3g) and trim5alpha, which restrict virus replication in monkey cells. variant hiv-1 molecular clones containing both a 21-nucleotide simian immunodeficiency virus (siv) gag ca element, corresponding to the hiv-1 cyclophilin a-binding site, and the entire siv vif gene were constructed. long-term passage ... | 2006 | 17065315 |
| safety and pharmacokinetics of intravaginal rings delivering tenofovir in pig-tailed macaques. | antiretroviral-based microbicides applied topically to the vagina may play an important role in protecting women from hiv infection. incorporation of the nucleoside reverse transcriptase inhibitor tenofovir (tfv) into intravaginal rings (ivrs) for sustained mucosal delivery may lead to increased microbicide product adherence and efficacy compared with those of conventional vaginal formulations. formulations of a novel "pod ivr" platform spanning a range of ivr drug loadings and daily release rat ... | 2012 | 22964245 |
| identification of the peptide-binding motif recognized by the pigtail macaque class i mhc molecule mane-a1*082:01 (mane a*0301). | rhesus and pigtail macaques have proven to be valuable animal models for several important human diseases, including hiv, where they exhibit similar pathology and disease progression. because rhesus macaques have been extensively characterized in terms of their major histocompatibility complex (mhc) class i alleles, their demand has soared, making them increasingly difficult to obtain for research purposes. this problem has been exacerbated by a continued export ban in place since 1978. pigtail ... | 2012 | 22278177 |
| multilineage polyclonal engraftment of cal-1 gene-modified cells and in vivo selection after shiv infection in a nonhuman primate model of aids. | we have focused on gene therapy approaches to induce functional cure/remission of hiv-1 infection. here, we evaluated the safety and efficacy of the clinical grade anti-hiv lentiviral vector, cal-1, in pigtailed macaques (macaca nemestrina). cal-1 animals exhibit robust levels of gene marking in myeloid and lymphoid lineages without measurable adverse events, suggesting that cal-1 transduction and autologous transplantation of hematopoietic stem cells are safe, and lead to long-term, multilineag ... | 2016 | 26958575 |
| the long-acting integrase inhibitor gsk744 protects macaques from repeated intravaginal shiv challenge. | daily preexposure prophylaxis (prep) with truvada is a proven hiv prevention strategy; however, its effectiveness is limited by low adherence. antiretroviral drug formulations that require infrequent dosing may increase adherence and thus prep effectiveness. we investigated whether monthly injections of a long-acting formulation of the hiv integrase inhibitor gsk1265744 (gsk744 la) prevented simian/human immunodeficiency virus (shiv) infection by vaginal challenge in macaques. female pigtail mac ... | 2015 | 25589631 |
| a simian human immunodeficiency virus with a nonfunctional vpu (deltavpushiv(ku-1bmc33)) isolated from a macaque with neuroaids has selected for mutations in env and nef that contributed to its pathogenic phenotype. | previous studies have shown that passage of nonpathogenic shiv-4 through a series of macaques results in the selection of variants of the virus that are capable of causing rapid subtotal loss of cd4(+) t cells and aids within 6-8 months following inoculation into pig-tailed macaques. using a pathogenic variant of shiv-4 known as shiv(ku-1bmc33), we reported that a mutant of this virus with the majority of the vpu deleted was still capable of causing profound cd4(+) t cell loss and neuroaids in p ... | 2001 | 11259196 |
| characterization of a simian human immunodeficiency virus encoding the envelope gene from the ccr5-tropic hiv-1 ba-l. | the tat, rev, vpu, and env genes from the monocytotropic ccr5-dependent hiv-1 ba-l isolate were substituted for homologous simian immunodeficiency virus (siv) sequences in the siv genome. the resultant shiv (shiv ba-l) replicated in ccr5-positive pm-1 cells but not in ccr5-negative cemx174 cells. infection of hos cells expressing different co-receptors showed shiv ba-l to be strictly ccr5-dependent. infection of pm-1 cells and rhesus peripheral blood mononuclear cells (pbmcs) was highly sensitiv ... | 2003 | 12843740 |
| repeated vaginal shiv challenges in macaques receiving oral or topical preexposure prophylaxis induce virus-specific t-cell responses. | preexposure prophylaxis (prep) for hiv prevention is a novel biomedical prevention method. we have previously modeled prep during rectal shiv exposures in macaques and identified that simian/human immunodeficiency virus chimera (shiv)-specific t-cell responses were induced in the presence of antiretroviral drugs, an observation previously termed t-cell chemo-vaccination. this report expands those initial findings by examining a larger group of macaques that were given oral or topical prep during ... | 2015 | 25886925 |
| robust suppression of env-shiv viremia in macaca nemestrina by 3-drug art is independent of timing of initiation during chronic infection. | nonhuman primates (nhps) are an important model organism for studies of hiv pathogenesis and preclinical evaluation of anti-hiv therapies. the successful translation of nhp-derived data to clinically relevant anti-hiv studies will require better understanding of the viral strains and nhp species used and their responses to existing antiretroviral therapies (art). | 2013 | 24025078 |
| positive selection of mc46-expressing cd4+ t cells and maintenance of virus specific immunity in a primate aids model. | despite continued progress in the development of novel antiretroviral therapies, it has become increasingly evident that drug-based treatments will not lead to a functional or sterilizing cure for hiv(+) patients. in 2009, an hiv(+) patient was effectively cured of hiv following allogeneic transplantation of hematopoietic stem cells (hscs) from a ccr5(-/-) donor. the utility of this approach, however, is severely limited because of the difficulty in finding matched donors. hence, we studied the ... | 2013 | 23719296 |
| characterisation of simian immunodeficiency virus-infected cells in pigtail macaques. | defining which cells become infected with simian immunodeficiency virus (siv) in vivo should assist in unravelling the pathogenesis of human immunodeficiency virus (hiv)/siv infection. hiv/siv infection of cd4(+) t cells resulted in down-regulation of cd3 and cd4 surface molecules in vitro, however this phenomenon is poorly characterised in vivo. intracellular siv p27 was studied by flow cytometry in serial blood samples and lymph node samples during acute infection of 17 sivmac-infected pigtail ... | 2012 | 22507218 |
| dynamics of envelope evolution in clade c shiv-infected pig-tailed macaques during disease progression analyzed by ultra-deep pyrosequencing. | understanding the evolution of the human immunodeficiency virus type 1 (hiv-1) envelope during disease progression can provide tremendous insights for vaccine development, and simian-human immunodeficiency virus (shiv) infection of non-human primate provides an ideal platform for such studies. a newly developed clade c shiv, shiv-1157ipd3n4, which was able to infect rhesus macaques, closely resembled primary hiv-1 in transmission and pathogenesis, was used to infect several pig-tailed macaques. ... | 2012 | 22427893 |
| naturally acquired mycobacterium tuberculosis complex in laboratory pig-tailed macaques. | here we present a case series from a primate research facility. the index case, a 4-year-old pig-tailed macaque (macaca nemestrina) experimentally infected with chimeric simian-human immunodeficiency virus (shivsf162 p4), developed weight loss and was euthanized. based on necropsy results the animal was diagnosed with opportunistic atypical mycobacteriosis associated with simian aids (saids). subsequently, tissues from the index animal, as well as tissues and oral mucosal swabs from six shiv-inf ... | 2012 | 26038402 |
| partial efficacy of a broadly neutralizing antibody against cell-associated shiv infection. | broadly neutralizing antibodies (bnabs) protect macaques from cell-free simian/human immunodeficiency virus (shiv) challenge, but their efficacy against cell-associated shiv is unclear. virus in cell-associated format is highly infectious, present in transmission-competent bodily fluids, and potentially capable of evading antibody-mediated neutralization. the pgt121 bnab, which recognizes an epitope consisting of the v3 loop and envelope glycans, mediates antibody-dependent cellular cytotoxicity ... | 2017 | 28794282 |