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.

Download full-text


Available from: Christopher James Miller
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The development of HIV vaccines has been hampered by the lack of an animal model that can accurately predict vaccine efficacy. Chimpanzees can be infected with HIV-1 but are not practical for research. However, several species of macaques are susceptible to the simian immunodeficiency viruses (SIVs) that cause disease in macaques, which also closely mimic HIV in humans. Thus, macaque-SIV models of HIV infection have become a critical foundation for AIDS vaccine development. Here we examine the multiple variables and considerations that must be taken into account in order to use this nonhuman primate (NHP) model effectively. These include the species and subspecies of macaques, virus strain, dose and route of administration, and macaque genetics, including the major histocompatibility complex molecules that affect immune responses, and other virus restriction factors. We illustrate how these NHP models can be used to carry out studies of immune responses in mucosal and other tissues that could not easily be performed on human volunteers. Furthermore, macaques are an ideal model system to optimize adjuvants, test vaccine platforms, and identify correlates of protection that can advance the HIV vaccine field. We also illustrate techniques used to identify different macaque lymphocyte populations and review some poxvirus vaccine candidates that are in various stages of clinical trials. Understanding how to effectively use this valuable model will greatly increase the likelihood of finding a successful vaccine for HIV. Curr. Protoc. Immunol. 102:12.14.1-12.14.30. © 2013 by John Wiley & Sons, Inc.
    Full-text · Article · Oct 2013 · Current protocols in immunology / edited by John E. Coligan ... [et al.]
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Nonhuman primate (NHP) disease models for AIDS have made important contributions to the search for effective vaccines for AIDS. Viral diversity, persistence, capacity for immune evasion, and safety considerations have limited development of conventional approaches using killed or attenuated vaccines, necessitating the development of novel approaches. Here we highlight the knowledge gained and lessons learned in testing vaccine concepts in different virus/NHP host combinations. © 2012 Cold Spring Harbor Laboratory Press; all rights reserved.
    Full-text · Article · Jun 2012 · Cold Spring Harbor Perspectives in Medicine
  • [Show abstract] [Hide abstract]
    ABSTRACT: Several nonhuman primate models are used in HIV/AIDS research. In contrast to natural host models, infection of macaques with virulent simian immunodeficiency virus (SIV) isolates results in a disease (simian AIDS) that closely resembles HIV infection and AIDS. Although there is no perfect animal model, and each of the available models has its limitations, a carefully designed study allows experimental approaches that are not feasible in humans, but that can provide better insights in disease pathogenesis and proof-of-concept of novel intervention strategies. In the early years of the HIV pandemic, nonhuman primate models played a minor role in the development of antiviral strategies. Since then, a better understanding of the disease and the development of better compounds and assays to monitor antiviral effects have increased the usefulness and relevance of these animal models in the preclinical development of HIV vaccines, microbicides, and antiretroviral drugs. Several strategies that were first discovered to have efficacy in nonhuman primate models are now increasingly used in humans. Recent trends include the use of nonhuman primate models to explore strategies that could reduce viral reservoirs and, ultimately, attempt to cure infection. Ongoing comparison of results obtained in nonhuman primate models with those observed in human studies will lead to further validation and improvement of these animal models so they can continue to advance our scientific knowledge and guide clinical trials.
    No preview · Article · Sep 2011 · AIDS research and human retroviruses
Show more