Roles of substrate availability and infection of resting and activated CD4+ T cells in transmission and acute simian immunodeficiency virus infection.
In studies of sexual mucosal transmission and early stages of simian immunodeficiency virus (SIV) and HIV infections, productive infection predominates in CD4(+) T cell populations, in both ostensibly resting and activated cells. The surprising ability of SIV and HIV to replicate in resting cells in vivo, in contrast to propagation of infection in vitro, suggested a model in which during the early stages of infection these viruses exploit the greater availability of resting cells to maintain unbroken chains of transmission from an infected resting cell to another resting cell nearby. Because immune activation in response to infection provides more activated CD4(+) T cells, these viruses take advantage of the greater efficiency of virus production and spread in activated cells for propagation and dissemination of infection. In this article, we report the results of experimental tests of this model, including visualization at the light microscopic level and direct analysis of virus production by cells in tissues. Analysis of tissues of rhesus macaques inoculated intravaginally or i.v. with SIV supports the proposed roles of target cell availability, susceptibility, and virus production by infected resting and activated CD4(+) T cells in mucosal transmission and early infection, and points to a potential role for topical anti-inflammatory agents in moderating the initial propagation of infection.
Zhang
Zhi-Qiang
ZQ
Department of Microbiology, University of Minnesota Medical School, MMC 196, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA.
Wietgrefe
Stephen W
SW
Li
Qingsheng
Q
Shore
Marta Dykhuizen
MD
Duan
Lijie
L
Reilly
Cavan
C
Lifson
Jeffrey D
JD
Haase
Ashley T
AT
D000208:Acute Disease; D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000821:virology*; D002584:Cervix Uteri / Q000821:virology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000276:immunology; D008198:Lymph Nodes / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology*; D008253:Macaca mulatta; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000821:virology; D012367:RNA, Viral / Q000032:analysis; D009418:S100 Proteins / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000635:transmission* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014771:Virion / Q000378:metabolism; D014779:Virus Replication; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D019394:Ki-67 Antigen; D012367:RNA, Viral; D009418:S100 Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule