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.

Viral kinetics in untreated versus treated acute HIV infection in prospective cohort studies in Thailand

“…These observations highlight the urgency of initiating ART as early as possible when acute infection is diagnosed. The VL kinetics observed in our studies are similar to the earlier acute simian immunodeficiency virus and HIV studies, which showed that VL levels and patterns were influenced by the available target cells and host immune responses [14][15][16]. The levels of viremia during the first week of acute infection and at set-point were highly correlated; the latter was a critical determinant for disease progression [1,15].…”

“…The VL kinetics observed in our studies are similar to the earlier acute simian immunodeficiency virus and HIV studies, which showed that VL levels and patterns were influenced by the available target cells and host immune responses [14][15][16]. The levels of viremia during the first week of acute infection and at set-point were highly correlated; the latter was a critical determinant for disease progression [1,15]. The decline from peak viremia was due mainly to the depletion of productively infected cells [14][15][16].…”

Multiple Hiv-1 Infection of Cells and the Evolutionary Dynamics of Cytotoxic T Lymphocyte Escape Mutants

“…Such findings have lead to the suggestion that CTL do not contribute significantly to virus control in these cases. This is in contrast to findings that link the decline of virus load in acute HIV-1 infection to the rise of CTL responses, and that correlate more vigorous CTL responses to lower setpoint virus loads and slower disease progression (Phillips et al 1991;Koenig et al 1995;Borrow et al 1997;Goulder et al 1997a;Lifson et al 1997). The evolutionary dynamics of CTL escape mutants appear to be more complex than those of drug-resistant virus strains, which tend to appear readily under the appropriate selection pressures.…”

Models of RNA virus evolution and their roles in vaccine design

“…At the beginning of the infection, before the immune response is mounted (a' ≈ 0), and after the initial peak of viral load, viruses and infected and uninfected cells reach a stable equilibrium termed viral set point (Figure 3). While monitoring viral load of SIV in infected macaques, a correlation between the viral load at initial stages of the infection and the viral set point was observed [152,153]. One can demonstrate that the equilibrium abundance of viruses, v*, and the logarithm of the virus load during the exponential growth phase, follow the linear relationship…”