title: The extent of early viral replication is a critical determinant of the natural history of simian immunodeficiency virus infection.
abstract: Different patterns of viral replication correlate with the natural history of disease progression in humans and macaques infected with human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV), respectively. However, the viral and host factors influencing these patterns of viral replication in vivo are poorly understood. We intensively studied viral replication in macaques receiving identical inocula of SIV. Marked differences in viral replication patterns were apparent within the first week following inoculation, a time prior to the development of measurable specific immune effector responses to viral antigens. Plasma viral RNA levels measured on day 7 postinoculation correlated with levels measured in the postacute phase of infection. Differences in the susceptibility of host cells from different animals to in vitro SIV infection correlated with the permissiveness of the animals for early in vivo viral replication and hence with the postacute set point level of plasma viremia. These results suggest that host factors that exert their effects prior to full development of specific immune responses are critical in establishing the in vivo viral replication pattern and associated clinical course in subjects infected with SIV and, by extension, with HIV-1.
authors.affiliation: AIDS Vaccine Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702, USA. lifson@avpvx1.ncifcrf.gov
authors.forename: J D
authors.initials: JD
authors.lastname: Lifson
authors.forename: M A
authors.initials: MA
authors.lastname: Nowak
authors.forename: S
authors.initials: S
authors.lastname: Goldstein
authors.forename: J L
authors.initials: JL
authors.lastname: Rossio
authors.forename: A
authors.initials: A
authors.lastname: Kinter
authors.forename: G
authors.initials: G
authors.lastname: Vasquez
authors.forename: T A
authors.initials: TA
authors.lastname: Wiltrout
authors.forename: C
authors.initials: C
authors.lastname: Brown
authors.forename: D
authors.initials: D
authors.lastname: Schneider
authors.forename: L
authors.initials: L
authors.lastname: Wahl
authors.forename: A L
authors.initials: AL
authors.lastname: Lloyd
authors.forename: J
authors.initials: J
authors.lastname: Williams
authors.forename: W R
authors.initials: WR
authors.lastname: Elkins
authors.forename: A S
authors.initials: AS
authors.lastname: Fauci
authors.forename: V M
authors.initials: VM
authors.lastname: Hirsch
mesh_terms: D000818:Animals; D008253:Macaca mulatta; D008254:Macaca nemestrina; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000503:physiopathology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014779:Virus Replication