Longitudinal follow up of SIVmac pathogenesis in rhesus macaques of Chinese origin: emergence of B cell lymphoma

Abstract

Two subspecies of rhesus (Rh) macaques, the Chinese (Ch) and Indian (Ind) subspecies were infected intravenously with 100TCID50 SIVmac239. CD4+, CD8+ T cells, plasma viral loads, depletion of intestinal lymphocytes with memory phenotype, humoral immune responses and clinical courses were monitored for 600 days. The pathogenesis of SIVmac was also compared with primary human immunodeficiency virus (HIV) infection of humans. Plasma viral loads in Ch Rh were lower in the acute and chronic phases compared with Ind Rh. SIVmac pathogenesis in Ch Rh was closer to virus loads in untreated HIV infected humans. Ch Rh had higher CD4/CD8 ratios, stronger antibody responses and interestingly, less depletion of intestinal memory CCR5+ CD4+ T lymphocytes compared with Ind Rh. One Ch Rh developed B cell origin lymphoma at 570 days post-infection, the first such report in this subspecies. Three of four Ind Rh developed AIDS within 6 months. The findings indicate that Ch Rh are more resistant to SIVmac pathogenesis compared with Ind Rh and that Ch Rh paralleled HIV-1 infections in untreated adult humans. The SIVmac infected Ch Rh subspecies are an acceptable model for HIV/AIDS.

Molecularly Cloned SHIV-1157ipd3N4: a Highly Replication- Competent, Mucosally Transmissible R5 Simian-Human Immunodeficiency Virus Encoding HIV Clade Cenv

“…This lack of a correlation is not surprising for outbred populations of primates and is consistent with the idea that systemic infection occurs once the mucosal virus inoculum exceeds a minimal dose (11). Although previous studies have shown that the set points of SIV or SHIV in Indian-origin rhesus monkeys are generally higher than in Chinese-origin rhesus monkeys, conflicting results on the peak viremia have been observed (32,33,48,56). Our data showed that the peak viremia of SHIV1157ipd3N4 was significantly higher in Indian-origin rhesus monkeys than in Chinese-origin rhesus monkeys.…”

Changes in Soluble Factor-Mediated CD8+Cell-Derived Antiviral Activity in Cynomolgus Macaques Infected with Simian Immunodeficiency Virus SIVmac251: Relationship to Biological Markers of Progression

“…Cynomolgus macaque and Chinese rhesus macaque SIV infection models provide the closest match to human HIV-1 infection and progression profiles (38,53,62), particularly with regard to the recently reported diversity of virus load set points in untreated HIV-1-infected patients (26,27,45,54,57).…”

Copy Number Variation of CCL3-like Genes Affects Rate of Progression to Simian-AIDS in Rhesus Macaques (Macaca mulatta)

“…Next we investigated whether differences in the distribution of CCL3L copy number alleles between populations could explain the previously reported slower simian-AIDS progression rates of Chinese-origin animals [2]–[5]. That is, given the association between higher CCL3L copy number and slower progression, we would expect Indian-origin macaques to have, on average, lower CCL3L copy numbers as compared with Chinese-origin macaques.…”

“…Population substructure is a potential confounding variable for our analysis as it has previously been shown that Chinese-origin animals tend to exhibit slower progression rates post-infection than Indian-origin animals [2]–[5]. In order to address this issue, we first validated population assignments of all individuals in our sample by genotyping 53 unlinked microsatellites and analyzing the data using the Bayesian clustering algorithm S tructure [26] and Principle Component Analysis (see Text S1; Figures S2 and S3).…”

“…We and several other research groups have reported substantial inter-individual variation in progression rates to simian-AIDS as well as population level differences between Chinese- and Indian-origin macaques [2]–[5]. Understanding the genetic basis of these individual and population differences is critical to building reliable animal models of human HIV infection and AIDS progression.…”