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Acute infection of Macaca nemestrina by human immunodeficiency virus type 1
L R Frumkin1, M B Agy, R W Coombs
1Department of Medicine, University of Washington, Seattle 98195.
Abstract:
The pigtail macaque (Macaca nemestrina) has a marked sensitivity to infection by simian immunodeficiency virus and human immunodeficiency virus type 2 (HIV-2). On this basis, we previously studied this species' susceptibility to HIV-1 and demonstrated infection in six macaques inoculated with either cell-associated HIV-1 or cell-free virus alone. This report expands upon our initial in vitro and in vivo findings. Five laboratory-adapted and one primary clinical strain of HIV-1 replicated in vitro in human and M. nemestrina peripheral blood mononuclear cells (PBMCs). Replication was enhanced when CD4+ purified PBMCs were infected and inhibited when PBMC cultures were treated with zidovudine. All six macaques demonstrated HIV-1 infection of PBMCs from 2 to 8 weeks after inoculation but nearly all PBMC cultures were negative from weeks 10 to 40. Polymerase chain reaction showed HIV-1 gag DNA in the PBMCs of all infected macaques, including times when the macaques were culture negative. All macaques developed and maintained antibodies to gag and envelope HIV-1 proteins from week 4 after inoculation through the period of observation. Five macaques showed neutralizing antibody. These findings suggest that M. nemestrina can be infected by cell-free and cell-associated HIV-1. This model of acute HIV-1 infection may help in evaluating the pathogenesis of HIV-1 replication and candidate vaccines and therapies.
Insights
Pigtail macaques (Macaca nemestrina) are susceptible to human immunodeficiency virus type 1 (HIV-1) infection. This study shows HIV-1 replicates in macaques, aiding vaccine and therapy research.
Area of Science:
- Virology
- Immunology
- Primatology
Background:
- Pigtail macaques (Macaca nemestrina) show sensitivity to simian immunodeficiency virus and HIV-2.
- Previous studies demonstrated Macaca nemestrina susceptibility to HIV-1.
Purpose of the Study:
- To expand on in vitro and in vivo findings of HIV-1 infection in Macaca nemestrina.
- To evaluate Macaca nemestrina as a model for HIV-1 pathogenesis, vaccine, and therapy research.
Main Methods:
- In vitro replication of laboratory-adapted and primary HIV-1 strains in human and Macaca nemestrina peripheral blood mononuclear cells (PBMCs).
- Inoculation of six macaques with cell-associated or cell-free HIV-1.
- Monitoring of viral replication, DNA presence (Polymerase Chain Reaction), and antibody development in macaques.
- Assessment of zidovudine's effect on PBMC cultures.
Main Results:
- HIV-1 replicated in vitro in both human and Macaca nemestrina PBMCs, enhanced in CD4+ cells and inhibited by zidovudine.
- All six macaques showed HIV-1 infection of PBMCs post-inoculation, with detectable HIV-1 gag DNA persisting even when cultures were negative.
- Macaques developed antibodies to HIV-1 gag and envelope proteins, with five showing neutralizing antibodies.
Conclusions:
- Macaca nemestrina can be infected by both cell-free and cell-associated HIV-1.
- This macaque model provides a valuable tool for studying acute HIV-1 infection, pathogenesis, and for evaluating candidate vaccines and therapies.