Open AccessVpx is required for dissemination and pathogenesis of SIVSM PBj: Evidence of macrophage-dependent viral amplification
Author(s) -
Vanessa M. Hirsch,
Mark E. Sharkey,
Charles R. Brown,
Beda Břicháček,
Simoy Goldstein,
John K. Wakefield,
Russell Byrum,
William R. Elkins,
Beatrice H. Hahn,
Jeffrey D. Lifson,
Mario Stevenson
Publication year - 1998
Publication title -
nature medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 19.536
H-Index - 547
eISSN - 1546-170X
pISSN - 1078-8956
DOI - 10.1038/3992
Subject(s) - simian immunodeficiency virus , virology , biology , virus , macrophage , viral replication , lentivirus , pathogenesis , mutant , in vitro , microbiology and biotechnology , gene , immunology , viral disease , genetics
The viral accessory protein Vpx is required for productive in vitro infection of macrophages by simian immunodeficiency virus from sooty mangabey monkeys (SIV(SM)). To evaluate the roles of Vpx and macrophage infection in vivo, we inoculated pigtailed macaques intravenously or intrarectally with the molecularly cloned, macrophage tropic, acutely pathogenic virus SIV(SM) PBj 6.6, or accessory gene deletion mutants (deltaVpr or deltaVpx) of this virus. Both wild-type and SIV(SM) PBj deltaVpx viruses were readily transmitted across the rectal mucosa. A subsequent 'stepwise' process of local amplification of infection and dissemination was observed for wild-type virus, but not for SIV(SM) PBj deltaVpx, which also showed considerable impairment of the overall kinetics and extent of its replication. In animals co-inoculated with equivalent amounts of wild-type and SIV(SM) Pbj deltaVpx intravenously or intrarectally, the deltaVpx mutant was at a strong competitive disadvantage. Vpx-dependent viral amplification at local sites of initial infection, perhaps through a macrophage-dependent mechanism, may be a prerequisite for efficient dissemination of infection and pathogenic consequences after exposure through either mucosal or intravenous routes.