Longitudinal analysis of monocyte/macrophage infection in simian immunodeficiency virus-infected, CD8+ T-cell-depleted macaques that develop lentiviral encephalitis.
The histopathological hallmark of lentiviral-associated encephalitis is an abundance of infected and activated macrophages. Why a subset of infected hosts develops lentiviral encephalitis and others do not is unknown. Using a CD8(+) T-cell depletion model of simian immunodeficiency virus (SIV)-infected rhesus macaques, we examined the relationship between peripheral SIV infection of monocytes/macrophages and the development of encephalitis. At the same time that cerebral spinal fluid viral load increased in macaques that developed encephalitis, we observed that monocyte-derived macrophages from these macaques produced more virus than those from macaques that did not develop encephalitis. However, during the course of infection, the number of blood monocyte-associated SIV DNA copies did not distinguish macaques that developed simian immunodeficiency virus encephalitis from macaques that did not develop encephalitis. Paradoxically, in this model, macaques that developed encephalitis had fewer SIV-infected macrophages in lungs and thymus at postmortem than macaques that did not develop encephalitis. These findings suggest that inherent differences in host monocyte viral production are related to development of encephalitis.
Bissel
Stephanie J
SJ
Department of Infectious Diseases and Microbiology, Graduate School of Public Health, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Wang
Guoji
G
Trichel
Anita M
AM
Murphey-Corb
Michael
M
Wiley
Clayton A
CA
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers; D001921:Brain; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D004279:DNA, Viral / Q000235:genetics*; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000134:cerebrospinal fluid / Q000276:immunology*; D008137:Longitudinal Studies; D008198:Lymph Nodes / Q000737:chemistry / Q000473:pathology*; D008253:Macaca mulatta; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology; D009928:Organ Specificity; D012367:RNA, Viral / Q000235:genetics*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000134:cerebrospinal fluid / Q000276:immunology* / Q000473:pathology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D019562:Viral Load; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D004279:DNA, Viral; D012367:RNA, Viral; C067980:CD68 antigen, human; D000097382:CD68 Molecule