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: 4.65). 01/2005; 78(24):14048-52. DOI: 10.1128/JVI.78.24.14048-14052.2004
Source: PubMed

ABSTRACT In rhesus macaques, classic systemic infection, characterized by persistent viremia and seroconversion, occurred after multiple low-dose (10(3) 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE OF REVIEW: Over the past decades, AIDS research has made tremendous progress in all key areas, including pathogenesis, prevention, and treatment. In particular, the introduction of potent antiretroviral therapy (ART) has dramatically reduced the morbidity and mortality of HIV-infected individuals. However, several challenges remain, including the absence of a vaccine that can reliably prevent virus acquisition, and the inability of current ART regimens to eradicate the infection. RECENT FINDINGS: Several key advances in HIV/AIDS research have been made possible by the extensive use of animal models and, in particular, the nonhuman primate models of SIV and SHIV infection of various monkey species including macaques, sooty mangabeys, vervets, and others. Key advantages of these models include the ability to control for parameters that are virtually impossible to assess in humans, to extensively study cells and tissues (including elective necropsy), and to perform proof-of-concept studies that would pose unacceptable safety risks in humans. SUMMARY: In this review, we describe the most recent advances in the use of animal models for HIV/AIDS research, and will break down these advances in three areas: models for virus transmission, dissemination, and pathogenesis; models for virus prevention and vaccines; and models for virus eradication and indefinite virus containment (functional cure) under ART.
    Current opinion in HIV and AIDS 04/2013; · 4.39 Impact Factor
  • Source
    PLoS Pathogens 05/2014; 10(5):e1004092. · 8.06 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To assess the efficacy of HIV vaccine candidates or preventive treatment, many research groups have started to challenge monkeys repeatedly with low doses of the virus. Such challenge data provide a unique opportunity to assess the importance of exposure history for the acquisition of the infection. I developed stochastic models to analyze previously published challenge data. In the mathematical models, I allowed for variation of the animals' susceptibility to infection across challenge repeats, or across animals. In none of the studies I analyzed, I found evidence for an immunizing effect of non-infecting challenges, and in most studies, there is no evidence for variation in the susceptibilities to the challenges across animals. A notable exception was a challenge experiment by Letvin et al. Sci Translat Med (2011) conducted with the strain SIVsmE660. The challenge data of this experiment showed significant susceptibility variation from animal-to-animal, which is consistent with previously established genetic differences between the involved animals. For the studies which did not show significant immunizing effects and susceptibility differences, I conducted a power analysis and could thus exclude a very strong immunization effect for some of the studies. These findings validate the assumption that non-infecting challenges do not immunize an animal - an assumption that is central in the argument that repeated low-dose challenge experiments increase the statistical power of preclinical HIV vaccine trials. They are also relevant for our understanding of the role of exposure history for HIV acquisition and forecasting the epidemiological spread of HIV.
    PLoS Computational Biology 11/2012; 8(11):e1002767. · 4.83 Impact Factor

Full-text (2 Sources)

Available from
May 22, 2014