Mucosal transmission of pathogenic CXCR4-utilizing SHIV(SF33A) variants in rhesus macaques

Janet M. Harouse, Rei Chin How Tan, Agegnehu Gettie, Peter Dailey, Preston A. Marx, Paul A Luciw, Cecilia Cheng-Mayer

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Infection of macaques with chimeric simian/human immunodeficiency virus (SHIV) expressing the envelope protein of HIV-1 provides a model system for studying HIV-1 infection in humans. To this end, four rhesus macaques (Macaca mulatta) were given a single intravaginal (IVAG) inoculation of cell-free SHIV(SF33A) and longitudinal samples of peripheral blood and lymph nodes were analyzed for viremia, antigenemia, and various T-cell populations. Rhesus macaques infected IVAG with SHIV(SF33A) demonstrated a dramatic decrease in the CD4+ PBMC subset in the initial weeks after viral exposure, a time that corresponded to peak in plasma viremia and antigenemia. Within 4 months of SHIV(SF33A) inoculation, partial to complete rebound of the CD4+ PBMC was seen in these animals. Notably, the regeneration of the CD4+ subset was associated with regeneration of the naive T-cell population and was concordant with clearance of plasma viremia. DNA heteroduplex tracking assays revealed transmission of minor variants within the SHIV(SF33A) inoculum to the IVAG-inoculated animals. The cell-free SHIV(SF33A) inoculum as well as virus isolated from animals early after transmission used the chemokine molecule CXCR4 as the primary cellular coreceptor, demonstrating that viruses expressing envelope glycoproteins of the syncytia inducing (SI) phonotype can be transported across the vaginal mucosa. Although none of the animals has yet to develop clinical symptoms of simian AIDS (SAIDS), infectious virus and viral nucleic acids could be persistently isolated from each animal. Furthermore, animals transfused with blood from IVAG-infected macaques drawn 2 weeks after inoculation suffered a more profound and sustained CD4+ T-cell loss, persistent plasma viremia, and the development of SAIDS in one animal, indicating that IVAG-passaged SHIV(SF33A) was pathogenic. Taken together, these results establish that a pathogenic CXCR4-utilizing SHIV(SF33A) species crossed the cervicovaginal mucosa. Different courses of infection in the IVAG versus transfusion animals suggest that host-mediated responses elicited upon transmission across mucosal barriers may serve to limit viral replication and delay disease progression in the IVAG-infected animals.

Original languageEnglish (US)
Pages (from-to)95-107
Number of pages13
JournalVirology
Volume248
Issue number1
DOIs
StatePublished - Aug 15 1998

Keywords

  • AIDS
  • Animal models
  • Chemokine receptors
  • Pathogenesis
  • Viral transmission

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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    Harouse, J. M., Tan, R. C. H., Gettie, A., Dailey, P., Marx, P. A., Luciw, P. A., & Cheng-Mayer, C. (1998). Mucosal transmission of pathogenic CXCR4-utilizing SHIV(SF33A) variants in rhesus macaques. Virology, 248(1), 95-107. https://doi.org/10.1006/viro.1998.9236