Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans.
The highly pathogenic simian immunodeficiency virus/HIV type 1 (SHIV) chimeric virus SHIV(DH12R) induces a systemic depletion of CD4(+) T lymphocytes in rhesus monkeys during the initial 3-4 weeks of infection. Nonetheless, high levels of viral RNA production continue unabated for an additional 2-5 months. In situ hybridization and immunohistochemical analyses revealed that tissue macrophage in the lymph nodes, spleen, gastrointestinal tract, liver, and kidney sustain high plasma virus loads in the absence of CD4(+) T cells. Quantitative confocal immunofluorescence analysis indicated that greater than 95% of the virus-producing cells in these tissues are macrophage and less than 2% are T lymphocytes. Interestingly, the administration of a potent reverse transcriptase inhibitor blocked virus production during the early T cell phase but not during the later macrophage phase of the SHIV(DH12R) infection. When interpreted in the context of HIV-1 infections, these results implicate tissue macrophage as an important reservoir of virus in vivo. They become infected during the acute infection, gradually increase in number over time, and can be a major contributor to total body virus burden during the symptomatic phase of the human infection.
Igarashi
T
T
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0460, USA.
Brown
C R
CR
Endo
Y
Y
Buckler-White
A
A
Plishka
R
R
Bischofberger
N
N
Hirsch
V
V
Martin
M A
MA
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D002678:Chimera; D004064:Digestive System / Q000473:pathology / Q000821:virology; D018450:Disease Progression; D004352:Drug Resistance, Microbial; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D016180:Lentivirus Infections / Q000473:pathology / Q000821:virology*; D008221:Lymphoid Tissue / Q000473:pathology / Q000821:virology; D008253:Macaca mulatta / Q000821:virology*; D008264:Macrophages / Q000821:virology*; D009928:Organ Specificity; D063065:Organophosphonates / Q000494:pharmacology; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000068698:Tenofovir; D019562:Viral Load; D014779:Virus Replication
D019380:Anti-HIV Agents; D063065:Organophosphonates; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine