Chinese-origin Rhesus Research Articles

Effects of treatment with suppressive combination antiretroviral drug therapy and the histone deacetylase inhibitor suberoylanilide hydroxamic acid; (SAHA) on SIV-infected Chinese rhesus macaques.

ObjectivesViral reservoirs–persistent residual virus despite combination antiretroviral therapy (cART)–remain an obstacle to cure of HIV-1 infection. Difficulty studying reservoirs in patients underscores the need for animal models that mimics HIV infected humans on cART. We studied SIV-infected Chinese-origin rhesus macaques (Ch-RM) treated with intensive combination antiretroviral therapy (cART) and 3 weeks of treatment with the histone deacetyalse inhibitor, suberoylanilide hydroxamic acid (SAHA).MethodsSIVmac251 infected Ch-RM received reverse transcriptase inhibitors PMPA and FTC and integrase inhibitor L-870812 beginning 7 weeks post infection. Integrase inhibitor L-900564 and boosted protease inhibitor treatment with Darunavir and Ritonavir were added later. cART was continued for 45 weeks, with daily SAHA administered for the last 3 weeks, followed by euthanasia/necropsy. Plasma viral RNA and cell/tissue-associated SIV gag RNA and DNA were quantified by qRT-PCR/qPCR, with flow cytometry monitoring changes in immune cell populations.ResultsUpon cART initiation, plasma viremia declined, remaining <30 SIV RNA copy Eq/ml during cART, with occasional blips. Decreased viral replication was associated with decreased immune activation and partial restoration of intestinal CD4+ T cells. SAHA was well tolerated but did not result in demonstrable treatment-associated changes in plasma or cell associated viral parameters.ConclusionsThe ability to achieve and sustain virological suppression makes cART-suppressed, SIV-infected Ch-RM a potentially useful model to evaluate interventions targeting residual virus. However, despite intensive cART over one year, persistent viral DNA and RNA remained in tissues of all three animals. While well tolerated, three weeks of SAHA treatment did not demonstrably impact viral RNA levels in plasma or tissues; perhaps reflecting dosing, sampling and assay limitations.

Development and validation of a SNP‐based assay for inferring the genetic ancestry of rhesus macaques (Macaca mulatta)

Rhesus macaques (Macaca mulatta) are an important primate model species in several areas of biomedical research. The wide geographic distribution of this species has led to significant genetic differentiation among local and regional populations. These regional differences can be important factors in the selection of the most appropriate subjects for particular research studies, as animals from different populations can respond differently to the same experimental treatment. Consequently, it is valuable to confirm the ancestry of individual rhesus monkeys from geographically distinct populations. Using DNA samples obtained from rhesus macaques from six National Primate Research Centers, we tested a set of 384 potential ancestry informative single nucleotide polymorphisms (SNPs) and identified a final panel of 91 SNPs that can reliably distinguish Indian-origin from Chinese-origin rhesus monkeys. This genetic test can be used to determine the ancestral origin of animals and to detect individuals that are hybrids between these two regional populations. To demonstrate use of the SNP panel, we investigated the ancestry of 480 animals from the Yerkes NPRC (YNPRC) for which the colony records were insufficient to clearly establish ancestry. Three of the YNPRC animals tested were determined to be hybrids. This SNP ancestry tool will be useful to researchers, colony managers, and others who wish to evaluate the ancestral origin of individual rhesus macaques, and therefore will facilitate more effective and efficient use of these animals in biomedical research.

Oral d-amphetamine increases sensitivity to negative consequences on an associative learning task in cocaine users

Oral d-amphetamine increases sensitivity to negative consequences on an associative learning task in cocaine users

Prophylactic and therapeutic effect of AZT/3TC in RT-SHIV infected Chinese-origin rhesus macaques

BackgroundThe precise efficacy of nucleoside analogue reverse-transcriptase inhibitors (NRTIs) in preventing and inhibiting virus replication remains unknown in RT-SHIV infected Chinese-origin rhesus macaques (Ch RM).FindingsCh RM were inoculated intravenously with 200 TCID50 RT-SHIV and treated by gavage with NRTIs (20 mg AZT and 10 mg 3TC twice per day) for four consecutive weeks beginning at one hour, on day 217 or 297 post inoculation, respectively. Treatment with AZT/3TC inhibited transiently RT-SHIV replication during chronic infection, but did not significantly affect peripheral blood CD4+ T cells in macaques. Treatment with AZT/3TC at 1 hour post infection prevented RT-SHIV infection in two out of four animals during the 120-day observation period.ConclusionsTherefore, the Ch RM model with RT-SHIV infection can be used to evaluate the efficacy of new NRTIs.

Yersinia pestis biovar Microtus strain 201, an avirulent strain to humans, provides protection against bubonic plague in rhesus macaques

Yersinia pestis biovar Microtus is considered to be a virulent to larger mammals, including guinea pigs, rabbits and humans. It may be used as live attenuated plague vaccine candidates in terms of its low virulence. However, the Microtus strain’s protection against plague has yet to be demonstrated in larger mammals. In this study, we evaluated the protective efficacy of the Microtus strain 201 as a live attenuated plague vaccine candidate. Our results show that this strain is highly attenuated by subcutaneous route, elicits an F1-specific antibody titer similar to the EV and provides a protective efficacy similar to the EV against bubonic plague in Chinese-origin rhesus macaques. The Microtus strain 201 could induce elevated secretion of both Th1-associated cytokines (IFN-γ, IL-2 and TNF-α) and Th2-associated cytokines (IL-4, IL-5, and IL-6), as well as chemokines MCP-1 and IL-8. However, the protected animals developed skin ulcer at challenge site with different severity in most of the immunized and some of the EV-immunized monkeys. Generally, the Microtus strain 201 represented a good plague vaccine candidate based on its ability to generate strong humoral and cell-mediated immune responses as well as its good protection against high dose of subcutaneous virulent Y. pestis challenge.

Large-scale polymorphism discovery in macaque G-protein coupled receptors

BackgroundG-protein coupled receptors (GPCRs) play an inordinately large role in human health. Variation in the genes that encode these receptors is associated with numerous disorders across the entire spectrum of disease. GPCRs also represent the single largest class of drug targets and associated pharmacogenetic effects are modulated, in part, by polymorphisms. Recently, non-human primate models have been developed focusing on naturally-occurring, functionally-parallel polymorphisms in candidate genes. This work aims to extend those studies broadly across the roughly 377 non-olfactory GPCRs. Initial efforts include resequencing 44 Indian-origin rhesus macaques (Macaca mulatta), 20 Chinese-origin rhesus macaques, and 32 cynomolgus macaques (M. fascicularis).ResultsUsing the Agilent target enrichment system, capture baits were designed for GPCRs off the human and rhesus exonic sequence. Using next generation sequencing technologies, nearly 25,000 SNPs were identified in coding sequences including over 14,000 non-synonymous and more than 9,500 synonymous protein-coding SNPs. As expected, regions showing the least evolutionary constraint show greater rates of polymorphism and greater numbers of higher frequency polymorphisms. While the vast majority of these SNPs are singletons, roughly 1,750 non-synonymous and 2,900 synonymous SNPs were found in multiple individuals.ConclusionsIn all three populations, polymorphism and divergence is highly concentrated in N-terminal and C-terminal domains and the third intracellular loop region of GPCRs, regions critical to ligand-binding and signaling. SNP frequencies in macaques follow a similar pattern of divergence from humans and new polymorphisms in primates have been identified that may parallel those seen in humans, helping to establish better non-human primate models of disease.

Major histocompatibility complex class I haplotype diversity in Chinese rhesus macaques.

The use of Chinese-origin rhesus macaques (Macaca mulatta) for infectious disease immunity research is increasing despite the relative lack of major histocompatibility complex (MHC) class I immunogenetics information available for this population. We determined transcript-based MHC class I haplotypes for 385 Chinese rhesus macaques from five different experimental cohorts, providing a concise representation of the full complement of MHC class I major alleles expressed by each animal. In total, 123 Mamu-A and Mamu-B haplotypes were defined in the full Chinese rhesus macaque cohort. We then performed an analysis of haplotype frequencies across the experimental cohorts of Chinese rhesus macaques, as well as a comparison against a group of 96 Indian rhesus macaques. Notably, 35 of the 51 Mamu-A and Mamu-B haplotypes observed in Indian rhesus macaques were also detected in the Chinese population, with 85% of the 385 Chinese-origin rhesus macaques expressing at least one of these class I haplotypes. This unexpected conservation of Indian rhesus macaque MHC class I haplotypes in the Chinese rhesus macaque population suggests that immunologic insights originally gleaned from studies using Indian rhesus macaques may be more applicable to Chinese rhesus macaques than previously appreciated and may provide an opportunity for studies of CD8+ T-cell responses between populations. It may also be possible to extend these studies across multiple species of macaques, as we found evidence of shared ancestral haplotypes between Chinese rhesus and Mauritian cynomolgus macaques.

Efficient Mucosal Transmissibility but Limited Pathogenicity of R5 SHIVSF162P3N in Chinese-Origin Rhesus Macaques

Infection of rhesus macaques (RMs) of Indian origin with simian immunodeficiency virus or simian-HIV (SHIV) provided powerful tools to study HIV-1 transmission and disease and for testing the efficacy of novel drugs, vaccines, and prevention strategies. In developing alternative nonhuman primate AIDS models for the CCR5 (R5)-tropic SHIVSF162P3N, we characterized virus transmission and infection in Chinese-origin RMs. Virologic, immunologic, and pathogenic evaluations of R5 SHIVSF162P3N infection in Chinese RMs challenged intrarectally (ir) or intravaginally were performed and compared with those previously observed in Indian-origin rhesus exposed to the same inoculum dose and via similar route. R5 SHIVSF162P3N transmits efficiently across mucosal surfaces in Chinese RMs. The magnitude and kinetics of early virus dissemination after ir inoculation in the Chinese macaques were similar to those observed in Indian rhesus, but a trend toward increased SHIVSF162P3N vaginal infectivity and rapid virus spread was seen in the Chinese macaques compared with the Indian-origin animals. Once infected, however, set point viremia in the ir- and intravaginal-infected Chinese rhesus was significantly lower and the animals survived longer compared with infected Indian rhesus. The R5 SHIVSF162P3N/Chinese RM infection model is suitable for studies of mucosal HIV-1 transmission and protection, but the high frequency of spontaneous control of chronic viremia and reduced virulence with SHIVSF162P3N in this macaque subspecies may limit its utility in studying HIV-1 pathogenesis and in evaluating vaccines and antiretrovirals that rely on reduction in chronic viral load or AIDS development as an experimental end point.

How well do you know your monkeys?

We read with interest the letter to the editor titled “How well do you know your monkey model” (1), written in response to our review article “The nonhuman primate model of tuberculosis” (J Med Primatol 41: 191–201) (2). This letter, by Engels and colleagues, raises an important issue about the use of the tuberculin skin test (TST) to detect Mycobacterium tuberculosis (Mtb) infection in nonhuman primates (NHPs). While we tend to agree with their general philosophy that improved detection of tuberculosis (TB), in particular latent TB, requires the development of more robust technologies, their understanding of our model is inherently flawed. The authors take for granted that all NHPs used in biomedical research are imported from nondomestic source countries. This is just not the case. The source of all Indian origin rhesus macaques in the US since the late 1970s has been from domestic breeding colonies. This was necessitated by a global ban on the export of Indian rhesus macaques by the government of India at that time. Since then, all Indian origin rhesus macaques at the NPRCs have been domestically bred and the animals are extremely well characterized with respect to infectious diseases such as tuberculosis (TB). As the authors state, rigorous preventive medicine programs have focused on maintaining negative TB status in domestic NHP colonies for many years. The authors are correct that the highest risk of TB infection in NHP occurs in animals imported from nondomestic sources. As a result, a best practice with respect to such animals is to keep them completely segregated from domestically bred NHPs. NHP originating from areas where TB is prevalent in the human population are extensively screened prior to inclusion at these NPRCs, or not used for TB research studies. Well-characterized domestic sources of NHP or NHP imported from areas without endemic TB are considered for these particular studies. It is the result of these strategies, that no TB outbreak has been detected at the TNPRC amongst domestically bred macaques, for more than two decades now. The author’s contention that “TST commonly fails to detect infection” is an overstatement, at least with respect to rhesus macaques. In an outbreak at the TNPRC close to 10 years ago in imported Chinese origin rhesus monkeys, the TST was diagnostic and was the screening method used to effectively identify cases and contain infection to a single room. Admittedly, adding other testing modalities increased our ability to confirm the diagnosis in this particular group of animals. The relatively low incidence of spontaneous TB cases in the literature compared to the number of domestic NHP used in research is a testament to the effectiveness of the TST used as a screening tool. If the TST “commonly” failed to detect cases of TB in domestic breeding colonies these colonies would have a much greater prevalence of disease than is currently noted. This contention is also supported by experimental data. In almost 125 Indian rhesus macaques experimentally infected since 2005, with Mtb CDC1551, H37Rv, Erdman or defined mutants of Mtb (3–8, unpublished results), here at the TNPRC, TST was able to detect Mtb infection. In many of these studies, which involved a vaccination component (6–8), TST always detected vaccination with BCG as well. In fact, we found no difference in the ability of TST and PRIMAGAM® (an interferon-gamma release assay comparable to QUANTIFERON-GOLD®) to detect experimental Mtb infection in domestically bred Indian rhesus at identical time-points. There is no argument that better TB diagnostic assays need to be developed and that the TST is far from a perfect screening tool. This is the driving force behind the development of nucleic acid based diagnostic tests for detecting human infections. However, the enthusiasm for such tests is dampened by the requirement for technology and infrastructure in resource-limited settings.

Mamu-B genes and their allelic repertoires in different populations of Chinese-origin rhesus macaques

Since rhesus monkeys of Chinese origin have gained greater utilization in recent years, it is urgent to investigate the major histocompatibility complex (MHC) immunogenetics of Chinese rhesus macaques. In this study, we identified 81 Mamu-B sequences using complementary DNA cloning and sequencing on a cohort of 58 rhesus monkeys derived from three local populations of China. Twenty of these Mamu-B alleles are novel and four of them represent new lineages. Although more alleles are shared among different populations than Mamu-A locus, the Mamu-B allelic repertoires found in these three populations of Chinese macaques are largely independent, which underscores the MHC polymorphism among different populations of Chinese rhesus macaques. Our results are an important addition to the limited MHC immunogenetic information available for rhesus macaques of Chinese origin.

Preliminary observations of MHC class I A region polymorphism in three populations of Chinese-origin rhesus macaques

Rhesus macaques are an animal model for the study of a variety of human diseases. The Chinese rhesus macaques have been widely used in biomedical research in recent years. However, the polymorphism of major histocompatibility complex (MHC) class I A region among different local populations of Chinese rhesus macaques has never been investigated. In this study, we identified 46 Mamu-A alleles by cDNA cloning and sequencing on a cohort of 53 Chinese rhesus monkeys including Zhiming, Chuanxi, and Fujian populations, of which 5 were first reported in rhesus monkeys. The frequencies of alleles were identified for each population. The result suggests that the repertoire of allelic variants of MHC class I A region found in different populations of Chinese macaques is largely non-overlapping. The frequencies of alleles and the popular allele are also different for different populations. PCR-SSP experiment further confirms the different frequencies of two alleles, Mamu-A*026:01 and Mamu-A*022:01, in additional 99 Zhiming monkeys and 191 Chuanxi monkeys. Our findings have important practical implications in that the origin of the individuals and the genetic polymorphism of the monkeys need to be considered at the level of local populations for Chinese rhesus monkeys in biomedical research. Further immunogenetic work is needed to investigate the MHC polymorphism among different populations of Chinese rhesus macaques and to reveal the functional implication of such polymorphism and disease outcome correlations.

HIV vaccine candidates generate in vitro T cell response to putative epitopes in Chinese-origin rhesus macaques

The Indian rhesus macaque is the established animal model for HIV infection and vaccine research. Growing evidence suggests that the more readily available Chinese rhesus macaque may be a more relevant option. As increasing numbers of novel Chinese rhesus MHC alleles are reported, we decided to explore potential HIV vaccine epitopes in this model. We immunized forty Chinese rhesus macaques with three different HIV vaccine candidates either individually or following a prime/boost strategy. We used ELISPOT to measure immune response in vitro to HIV-1 p24C and HIV-1 gp160 peptide libraries. We identified five putative epitopes with associations to HLA-I alleles including HLA*B-2705 and HLA-B*5101 (associated with slow disease progression and low viral set point) and HLA-B*18 (associated with rapid disease progression and high viral set point). This suggests the possible use of Chinese rhesus macaques to model different disease progressions. We also explored the use of fusion proteins as stimulators in ELISPOT assays. While PBMCs from 6 monkeys responded to peptide stimulation, PBMCs from 28 monkeys responded to the anthrax lethal factor fusion proteins LFn p24C and/or LFn gp140C. Our results support the use of Chinese rhesus macaques in HIV vaccine studies.

Variability of Bio-Clinical Parameters in Chinese-Origin Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Nonhuman Primate AIDS Model

BackgroundAlthough Chinese-origin Rhesus macaques (Ch RhMs) infected with simian immunodeficiency virus (SIV) have been used for many years to evaluate the efficacy of AIDS vaccines and therapeutics, the bio-clinical variability of such a nonhuman primate AIDS model was so far not established.Methodology/Principal FindingsBy randomizing 150 (78 male and 72 female) Ch RhMs with diverse MHC class I alleles into 3 groups (50 animals per group) challenged with intrarectal (ir) SIVmac239, intravenous (iv) SIVmac239, or iv SIVmac251, we evaluated variability in bio-clinical endpoints for 118 weeks. All SIV-challenged Ch RhMs became seropositive for SIV during 1–2 weeks. Plasma viral load (VL) peaked at weeks 1–2 and then declined to set-point levels as from week 5. The set-point VL was 30 fold higher in SIVmac239 (ir or iv)-infected than in SIVmac251 (iv)-infected animals. This difference in plasma VL increased overtime (>100 fold as from week 68). The rates of progression to AIDS or death were more rapid in SIVmac239 (ir or iv)-infected than in SIVmac251 (iv)-infected animals. No significant difference in bio-clinical endpoints was observed in animals challenged with ir or iv SIVmac239. The variability (standard deviation) in peak/set-point VL was nearly one-half lower in animals infected with SIVmac239 (ir or iv) than in those infected with SIVmac251 (iv), allowing that the same treatment-related difference can be detected with one-half fewer animals using SIVmac239 than using SIVmac251.Conclusion/SignificanceThese results provide solid estimates of variability in bio-clinical endpoints needed when designing studies using the Ch RhM SIV model and contribute to the improving quality and standardization of preclinical studies.

SIV-infected Chinese-origin rhesus macaques express specific MHC class I alleles in either elite controllers or normal progressors

SIV-infected Chinese-origin rhesus macaques express specific MHC class I alleles in either elite controllers or normal progressors

Chinese origin rhesus macaque major histocompatibility complex class I molecules promiscuously present epitopes from SIV associated with molecules of Indian origin; implications for immunodominance and viral escape

The presentation of identical peptides by different major histocompatibility complex class I (MHC-I) molecules, termed promiscuity, is a controversial feature of T cell-mediated immunity to pathogens. The astounding diversity of MHC-I molecules in human populations, presumably to enable binding of equally diverse peptides, implies promiscuity would be a rare phenomenon. However, if it occurs, it would have important implications for immunity. We screened 77 animals for responses to peptides known to bind MHC-I molecules that were not expressed by these animals. Some cases of supposed promiscuity were determined to be the result of either non-identical optimal peptides or were simply not mapped to the correct MHC-I molecule in previous studies. Cases of promiscuity, however, were associated with alterations of immunodominance hierarchies, either in terms of the repertoire of peptides presented by the different MHC-I molecules or in the magnitude of the responses directed against the epitopes themselves. Specifically, we found that the Mamu-B*017:01-restricted peptides Vif HW8 and cRW9 were also presented by Mamu-A2*05:26 and targeted by an animal expressing that allele. We also found that the normally subdominant Mamu-A1*001:01 presented peptide Gag QI9 was also presented by Mamu-B*056:01. Both A2*05:26 and B*056:01 are molecules typically or exclusively expressed by animals of Chinese origin. These data clearly demonstrate that MHC-I epitope promiscuity, though rare, might have important implications for immunodominance and for the transmission of escape mutations, depending on the relative frequencies of the given alleles in a population.

Histopathological Observation of Immunized Rhesus Macaques with Plague Vaccines after Subcutaneous Infection of Yersinia pestis

In our previous study, complete protection was observed in Chinese-origin rhesus macaques immunized with SV1 (20 µg F1 and 10 µg rV270) and SV2 (200 µg F1 and 100 µg rV270) subunit vaccines and with EV76 live attenuated vaccine against subcutaneous challenge with 6×106 CFU of Y. pestis. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological and immunohistochemical techniques. In addition, the glomerular basement membranes (GBMs) of the immunized animals and control animals were checked by electron microscopy. The results show no signs of histopathological lesions in the lungs, livers, kidneys, lymph nodes, spleens and hearts of the immunized animals at Day 14 after the challenge, whereas pathological alterations were seen in the corresponding tissues of the control animals. Giemsa staining, ultrastructural examination, and immunohistochemical staining revealed bacteria in some of the organs of the control animals, whereas no bacterium was observed among the immunized animals. Ultrastructural observation revealed that no glomerular immune deposits on the GBM. These observations suggest that the vaccines can effectively protect animals from any pathologic changes and eliminate Y. pestis from the immunized animals. The control animals died from multi-organ lesions specifically caused by the Y. pestis infection. We also found that subcutaneous infection of animals with Y. pestis results in bubonic plague, followed by pneumonic and septicemic plagues. The histopathologic features of plague in rhesus macaques closely resemble those of rodent and human plagues. Thus, Chinese-origin rhesus macaques serve as useful models in studying Y. pestis pathogenesis, host response and the efficacy of new medical countermeasures against plague.

Frequency of the major histocompatibility complex Mamu‐A*01 allele in experimental rhesus macaques in China

In Indian rhesus macaques, the major histocompatibility complex Mamu gene, especially the Mamu-A*01 allele, plays an important role in simian immunodeficiency virus susceptibility and disease progression. The Mamu-A*01 allele is one of the protective genes mostly being studied in simian acquired immunodeficiency syndrome. PCR was used to amplify the Mamu-A*01 allele in 130 Chinese-origin rhesus macaques. Identification of the allele was then confirmed by sequencing and IFN-γ ELISPOT assay. The Mamu-A*01 allele was detected in 3.85% (5 of 130) of the experimental Chinese-origin rhesus macaques. The sequence homology reached 99.1% in comparison with Indian rhesus macaques. A significantly large number of spots were observed in Mamu-A*01-positive monkeys when analyzed by ELISPOT with Gag181-189 epitope stimulation. Our study suggests that Mamu-A*01-positive Chinese-origin rhesus monkeys are suitable for use in AIDS studies.

Comparison of Immunological Responses of Plague Vaccines F1 + rV270 and EV76 in Chinese-Origin Rhesus Macaque, Macaca mulatta

The subunit vaccine SV1 (20 μg F1+10 μg rV270) has been identified as the optimal formulation in mice, which provided a good protection against plague in mice, guinea pigs and rabbits. To compare SV1 and SV2 (200 μg F1+100 μg rV270) with live attenuated vaccine EV76, antibody responses, protective efficacy, cytokines (IFN-γ, TNF-α, IL-2, IL-4, IL-10 and IL-12) production, CD4/CD8 ratio and CD69(+) T-cell activation marker were determined in sera of the immunized Chinese-origin rhesus macaques, Macaca mulatta. The immunized animals with SV1 or SV2 developed higher anti-rV270 IgG titre, while those immunized with EV76 elicited a negligible IgG to V antigen, indicating that subunit vaccine (SV) had an advantage over EV76 in terms of the indispensable role of anti-V antibody against Yersinia pestis. There was no significant antibody titre difference between SV1 and SV2, suggesting that the immune response may have been saturated at the dose level of SV1. There were no statistical changes for CD4/CD8 ratios, IL-4 and CD69 levels between the three-vaccine immunized groups. However, a significant higher level of IL-12 was observed in the EV76 immunized animals, indicating that EV76 had an advantage over SV in respect of cellular immunity. Complete protection was observed for the immunized animals with SV and EV76, revealing that SV has a similar protective efficacy with EV76 against 6×10⁶ CFU of Y. pestis challenge by subcutaneous route in Chinese-origin rhesus macaques.

Serial passage of clade C SHIV-XJ02170 in Chinese origin Rhesus macaques

Objective To analyze the virologic and immunologic properties during SHIV-XJ02170passage in vivo and construct the clade C SHIV/Chinese origin Rhesus macaques AIDS model . Methods SHIV-XJ02170 cell-free virus tranfected in 293T was adapted by serial passage in nine Chinese-origin Rhesus macaques. CD4/CD8 ratio was detected by flow cytometry to analyze the changes in viral pathogenicity. Real-time RT-PCR and IFN-γsecreting ELISPOT methods were used to analyze changes in characteristics of virology and immunology. Results During in vivo passage, CD4/CD8 ratio did not deeply decline. However,the peak and setpoint viral load in the line 3 show a continuous upward trend. The strong humoral and cellular immune responses were induced after SHIV-XJ02170 infection. Meanwhile, there was significant positive correlation between the viral load and binding antibody titer. Conclusion There were no pathogenic viral strains, and upward trend in virulence of SHIV-XJ02170 was found during in vivo passaging. SHIVXJ02170/Chinese origin Rhesus macaques model will play an important role in effect evaluation of candidate AIDS vaccines in China. Key words: SHIV; Passage; Rhesus macaques; Model

Eight novel MHC class I alleles identified in Chinese‐origin rhesus macaques

We report here the identification of four Mamu-A1 and four Mamu-B novel alleles of Chinese-origin rhesus macaques.