Mucosal Transmission of Pathogenic CXCR4-Utilizing SHIVSF33AVariants in Rhesus Macaques

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...

Full description

Saved in:
Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 1998-08, Vol.248 (1), p.95-107
Main Authors: Harouse, Janet M., Tan, Rei Chin How, Gettie, Agegnehu, Dailey, Peter, Marx, Preston A., Luciw, Paul A., Cheng-Mayer, Cecilia
Format: Article
Language:English
Subjects:
AIDS
animal models
chemokine receptors
pathogenesis
viral transmission
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 SHIVSF33Aand longitudinal samples of peripheral blood and lymph nodes were analyzed for viremia, antigenemia, and various T-cell populations. Rhesus macaques infected IVAG with SHIVSF33Ademonstrated 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 SHIVSF33Ainoculation, 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 SHIVSF33Ainoculum to the IVAG-inoculated animals. The cell-free SHIVSF33Ainoculum 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) phenotype 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 SHIVSF33Awas pathogenic. Taken together, these results establish that a pathogenic CXCR4-utilizing SHIVSF33Aspecies 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.
ISSN:0042-6822
1096-0341
DOI:10.1006/viro.1998.9236