Comparison of early plasma RNA loads in different macaque species and the impact of different routes of exposure on SIV/SHIV infection

Abstract

Various simian immunodeficiency virus (SIV)sm/mac and simian/human immunodeficiency virus (SHIV) strains are used in different macaque species to study AIDS pathogenesis, as well as to evaluate candidate vaccine and anti-retroviral drugs efficacy. In this study we investigated the effect of route of infection, species of macaques and nature of virus stock on early plasma viral RNA load. We monitored the plasma RNA concentrations of 63 rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis) infected with well-characterised virus stocks administered either by oral, rectal, vaginal or intravenous (i.v.) routes. In SIV(mac)-infected macaques, no significant difference in plasma RNA loads was observed between the rectal, oral and i.v. routes of infection. Cynomolgus macaques developed lower steady state SIV plasma RNA concentrations compared with rhesus macaques and no significant difference was observed between rectal and i.v. routes of infection. In SHIV(89.6p)-infected macaques, no difference between species or between route of infection was observed with this particular chimeric virus.

Long-Term Control of Simian Immunodeficiency Virus (SIV) in Cynomolgus Macaques Not Associated with Efficient SIV-Specific CD8+T-Cell Responses

“…In contrast to the rapid-progression macaque models of SIV infection, the SIVmac 251 infection model of CyM closely resembles HIV infection in humans in terms of viral load, CD4 ϩ T-cell depletion, and rates of progression (39). Thus, it appears to be an optimal model to study host mechanisms able to naturally control infection.…”

Unusually High Frequency MHC Class I Alleles in Mauritian Origin Cynomolgus Macaques

“…Previous work has shown that Cynomolgus macaques generally (65,66), and Mauritian origin Cynomolgus macaques in particular (67)(68)(69), can be infected with pathogenic SIV and develop sAIDS. When compared with Indian Rhesus macaques, Cynomolgus macaques require a higher dose of virus to consistently establish SIV infection (68) and maintain lower viral loads more similar to HIV-infected humans (66). This could complicate the evaluation of vaccines that seek to reduce set point viral load because differences between vaccinees and naive controls may be more difficult to detect.…”

Viral Dynamics during Primary Simian Immunodeficiency Virus Infection: Effect of Time-Dependent Virus Infectivity

“…Primary simian immunodeficiency virus (SIV)/HIV-1 infection has been studied both experimentally and via modeling (3,6,8,13,15,25,32,33,36,37,39,44). However, none of the within-host models in these studies has considered the time variation of virus infectivity.…”

“…As suggested by Ma et al (26), the highly infectious virus during the early phase compared to the chronic phase could be due to (i) insufficient rounds of replication during the early phase to produce enough noninfectious viral genomes; (ii) coating of the set-point phase plasma virions with antibodies that interfere with infectivity; and/or (iii) efficient elimination during early-phase infection of less-infectious genomes. Preliminary data comparing the ratio of the 50% tissue culture infectious dose (TCID 50 ) with HIV RNA copy number also suggests a decrease of virus infectivity over time during primary infection in HIV-1-infected patients (David Montefiori, Duke University School of Medicine, unpublished data).Primary simian immunodeficiency virus (SIV)/HIV-1 infection has been studied both experimentally and via modeling (3,6,8,13,15,25,32,33,36,37,39,44). However, none of the within-host models in these studies has considered the time variation of virus infectivity.…”