Rapid and irreversible CD4+ T-cell depletion induced by the highly pathogenic simian/human immunodeficiency virus SHIV(DH12R) is systemic and synchronous.
Highly pathogenic simian/human immunodeficiency virus chimeric viruses are known to induce a rapid, irreversible depletion of CD4+ T lymphocytes in the peripheral blood of acutely infected macaque monkeys. To more fully assess the systemic effects of this primary virus infection, specimens were collected serially between days 3 and 21 postinfection from variety of lymphoid tissues (lymph nodes, thymus, and spleen) and gastrointestinal tract and examined by DNA and RNA PCR, in situ hybridization, and immunohistochemical assays. In addition, the lymphoid tissues were evaluated by fluorescence-activated cell sorting. Virus infection was initially detected by DNA PCR on day 3 postinfection in lymph node samples and peaked on day 10 in the T-lymphocyte-rich areas of this tissue. CD4+ T-cell levels remained stable through day 10 in several lymphoid tissue specimens examined but fell precipitously between days 10 and 21. In situ terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assays revealed the accumulation of apoptotic cells during the second week of infection in both lymph nodes and thymus, which colocalized, to a large extent, to sites of both virus replication and CD4+ T-lymphocyte loss.
Igarashi
Tatsuhiko
T
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Brown
Charles R
CR
Byrum
Russell A
RA
Nishimura
Yoshiaki
Y
Endo
Yasuyuki
Y
Plishka
Ronald J
RJ
Buckler
Charles
C
Buckler-White
Alicia
A
Miller
Georgina
G
Hirsch
Vanessa M
VM
Martin
Malcolm A
MA
D000818:Animals; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002452:Cell Count; D004195:Disease Models, Animal; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity; D007150:Immunohistochemistry; D008221:Lymphoid Tissue / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta; D011995:Recombination, Genetic; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity; D013997:Time Factors