Document 0421
 DOCN  M9490421
 TI    Immune activation and viral burden in acute disease induced by simian
       immunodeficiency virus SIVsmmPBj14: correlation between in vitro and in
       vivo events.
 DT    9411
 AU    Schwiebert R; Fultz PN; Department of Microbiology, University of
       Alabama at Birmingham; 35294.
 SO    J Virol. 1994 Sep;68(9):5538-47. Unique Identifier : AIDSLINE
       MED/94335066
 AB    The simian immunodeficiency virus SIVsmmPBj14 (SIV-PBj14) is an atypical
       lentivirus that causes acute disease and death in pig-tailed macaques
       and in vitro replicates efficiently in resting macaque lymphocytes and
       activates and induces proliferation of lymphocytes. The present study
       was conducted to test the hypothesis that production of large quantities
       of SIV-PBj14 induces widespread immune activation and elaboration of
       cytokines which lead directly to the death of infected pig-tailed
       macaques. Following intravenous inoculation of pig-tailed macaques with
       SIV-PBj14, acute disease developed and was characterized by high levels
       of plasma viremia, p27gag antigenemia, tumor necrosis factor alpha, and
       interleukin-6 (IL-6). All animals died within 10 days of infection, at
       which time some animals had as many as 100% CD4+ cells in the periphery
       and lymphoid tissues infected. During the last few days before death,
       titers of infectious virus in blood increased as much as 10(5)-fold. By
       using dual-label immunofluorescence assays for detection of cell surface
       activation markers, both CD4+ and CD8+ lymphocytes were shown to express
       the IL-2 and transferrin receptors following either in vivo or in vitro
       infection with SIV-PBj14. Furthermore, in vitro infection of quiescent
       macaque lymphocytes by SIV-PBj14 was accompanied by proliferation of
       both CD4+ and CD8+ lymphocyte subsets, as measured by incorporation of
       [3H]thymidine. Increases in numbers of activated lymphocytes and levels
       of proinflammatory cytokines in plasma coincided with increased amounts
       of detectable virus in vivo. Clinical signs of disease and pathologic
       findings were most consistent with death from a shock-like syndrome, in
       which acute-phase inflammatory cytokines are known to play a major role.
       Tumor necrosis factor alpha, IL-2, and IL-6 were detected in some
       cultures infected with SIV-PBj14, but this finding was not consistent.
       When cytokines were detected, their concentrations were essentially no
       different from those found in control cultures infected with SIVsmm9, a
       prototypic strain from which SIV-PBj14 was derived. The in vivo results
       suggest a synergistic cycle of activation of lymphocytes and monocytes,
       elaboration of cytokines, and virus production that accelerates
       uncontrolled and culminates in death. The observed correlations between
       in vivo and in vitro activation events following SIV-PBj14 infection
       validate the use of in vitro studies to clarify lentivirus-lymphocyte
       interactions that may contribute to the virulence of SIV-PBj14.
 DE    Animal  Antigens, CD/ANALYSIS  Antigens, Differentiation,
       B-Lymphocyte/ANALYSIS  CD4-CD8 Ratio  Interleukin-6/METABOLISM
       Lymphocyte Transformation  Macaca nemestrina  Receptors,
       Interleukin-2/ANALYSIS  Simian Acquired Immunodeficiency
       Syndrome/*IMMUNOLOGY/  MICROBIOLOGY  Support, U.S. Gov't, P.H.S.
       SIV/*IMMUNOLOGY  Tumor Necrosis Factor/METABOLISM  Virus Replication
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).