Replication and Pathogenesis: A Comparative Lentiviral Perspective
Analyses of temporal and quantitative aspects of HIV-1 ribonucleic acid (RNA) in plasma before and after the institution of highly active antiretroviral therapy (HAART) have led to the realization that HIV-1 replication is highly dynamic in vivo, supplanting earlier notions that too little virus existed to account for the severity of the disease.31-35 Plasma viral RNA will decrease by approximately 2 log units within 2 weeks of instituting HAART.
Various estimates derived from such studies place the half-life of HIV-1 virions in vivo on the order of minutes to a few hours.31-33 The half-life of productively infected cells is also very short, approximately a day or two. Most plasma virus is produced quite recently.31-33 The relationship of viral load to HIV-1 to prognosis has been made clear in numerous studies.36,37 Individual patients reliably establish a particular viral “set point,” in which the plasma viral load remains fairly consistent over time within half a log unit after the resolution of the primary infection. Viral loads can exceed 107 RNA copies per ml of plasma during primary infection; set point values average between 104 and 105 but vary an order of magnitude or more in each direction. A single measurement of plasma RNA before treatment reliably reflects the steady state and also strongly predicts the rate of CD4+ lymphocyte depletion and progression to AIDS and death.36,37 Regardless of the starting level, however, viremia can be reliably suppressed to undetectable (chronic disease outcomes.20 For example, most EIAV-infected animals survive and progress from a 1- to 12-month chronic phase characterized by recurring bouts of viremia, fever, and hemolytic anemia to an extended asymptomatic stage.19 The chronic stage is characterized by very high titers of circulating cell-free virus. The virus also may impair the differentiation of erythroid precursors.20,53 In the generally asymptomatic carrier state that follows the chronic phase, only quite low levels of EIAV replication can be detected.54MVV and caprine arthritis-encephalitis virus (CAEV) replicate preferentially in macrophages rather than in circulating leukocytes, resulting in little cell-free viremia.55-57 Their genetic diversity suggests that they undergo considerable replication chronically.20 The arthritis seen in CAEV- infected goats resembles human rheumatoid arthritis in many respects.58