A Period of Transient Viremia and Occult Infection Precedes Persistent Viremia and Antiviral Immune Responses during Multiple Low-Dose Intravaginal Simian Immunodeficiency Virus Inoculations

California National Primate Research Center, University of California Davis, CA, USA.
Journal of Virology (Impact Factor: 4.44). 01/2005; 78(24):14048-52. DOI: 10.1128/JVI.78.24.14048-14052.2004
Source: PubMed


In rhesus macaques, classic systemic infection, characterized by persistent viremia and seroconversion, occurred after multiple
low-dose (103 50% tissue culture infective doses) intravaginal (IVAG) inoculations with simian immunodeficiency virus (SIV) strain SIVmac251.
Monkeys developed classic SIV infections after a variable number of low-dose IVAG exposures to SIVmac251. Once established,
the systemic infection was identical to SIV infection following high-dose IVAG SIV inoculation. However, occult systemic infection
characterized by transient cell-associated or cell-free viremia consistently occurred early in the series of multiple vaginal
SIV exposures. Further, antiviral cellular immune responses were present prior to the establishment of a classic systemic
infection in the low-dose vaginal SIV transmission model.

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Available from: Christopher James Miller, Oct 06, 2015
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    • "This is likely because the virus is subverting normal trafficking patterns of intraepithelial dendritic cells that bring antigen to immune inductive sites (regional lymph nodes), which are lacking in the vaginal mucosa as compared with intestinal mucosa. Although SIV can be found in draining lymph nodes within 18 h of vaginal inoculation, it is interesting to note that a delay in viremia often occurs with mucosal inoculation compared with intravenous inoculations of macaques (Ma et al. 2004; Miller et al. 2005). This likely occurs because the virus has to replicate locally for a period of time to generate sufficient progeny to cause a spreading infection or, in the case of the vagina, because of the low density of primary target cells that would be found in a regional lymph node. "
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    • "Furthermore, no SIV gag DNA was detected in the lymph nodes of the six animals with blips (data not shown). Such blips in plasma virus might reflect controlled or aborted infections, as have been reported [39], [40], [41], [42], [43], [44]. Since blips occurred across the different treatment groups, comparisons have been made based on the frequency of animals with typical viremia (not protected) versus those with undetectable virus or virus blips (protected). "
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    • "In the present study, the detected viral-specific T-cell responses (vSTRs) that persistently appeared earlier following the first few mucosal challenges did not result in protection from subsequent viral challenges. Another repeated-challenge study utilizing SIV mac251 reported a sporadic appearance of either Tcell proliferation or low-level Gag specific responses during a period of occult infection, prior to the period of persistent viremia (Ma et al., 2004). The presence of peripheral vSTRs prior to detection of plasma vRNA was observed in 3 of the four animals that became infected by week six (control 1, placebo 1 and DC-SIGN 2) (Fig. 4A). "
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