SIVmac251 Is Inefficiently Transmitted to Rhesus Macaques by Penile Inoculation with a Single SIV env Variant Found in Ramp-up Phase Plasma

Center for Comparative Medicine, University of California, Davis, USA.
AIDS research and human retroviruses (Impact Factor: 2.33). 07/2011; 27(12):1259-69. DOI: 10.1089/aid.2011.0090
Source: PubMed


Abstract Despite the fact that approximately half of all HIV patients acquire infection through penile exposure, there have been no recent studies of penile SIV transmission in rhesus macaques and the nature of the virus variants transmitted, target cells, and pathways of virus dissemination to systemic lymphoid tissues are not known. Single genome amplification (SGA) and sequencing of HIV-1 RNA in plasma of acutely infected humans allows the identification and enumeration of transmitted/founder viruses responsible for productive systemic infection. Studies using the SGA strategy have shown that intrarectal and intravaginal SIV transmission to macaques recapitulates key features of human HIV transmission. To date, no studies have used the SGA assay to identify transmitted/founder virus(es) in macaques infected after penile SIV exposure. Here we report that SIV can be transmitted by penile SIV exposure. However, similar exposure to a high-dose inoculum infects only about half the animals, which is about 50% less efficient transmission than occurs after vaginal SIV challenge. In addition, only a single SIV env variant established the systemic infection in all five animals that became infected after penile exposure, a result that is consistent with low incidence and few transmitted HIV variants in heterosexually infected men. Our results suggest that the penile transmission of SIVmac251 in rhesus macaques recapitulates the key features of penile HIV-1 transmission and may provide insight into host or viral factors that permit penile transmission and dissemination. Furthermore, this SIV challenge exposure route will be useful in testing vaccines and other prophylactic approaches.

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    • "In addition, antibiotic treatment to resolve bacterial vaginosis and reduce inflammation can be beneficial. A penile model for SIV transmission was recently developed by immersing the penis into cell-free virus, but this mode of transmission is much less efficient than vaginal exposure and requires higher doses of virus to establish the infection (Ma et al., 2011). This finding is consistent with epidemiological data in discordant monogamous couples where the rate of male to female HIV transmission was greater than female to male (Padian et al., 1997; Gray et al., 2001). "
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    • "Antiviral immune responses operative in primate lentivirus infection can be considered as (1) intrinsic (Malim and Bieniasz 2011), (2) innate (Carrington and Alter 2011), or (3) adaptive, comprising both humoral (Overbaugh and Morris 2011) and cellular (Walker and McMichael 2011) immunity. For each response, there is evidence that lentiviruses evolve countermeasures to overcome host mechanisms. "
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