Molecular Interactions among Herpesviruses and Human Immunodeficiency Viruses

Abstract

The average interval between human immunodeficiency virus (HIV) infection of an adult through sexual intercourse or blood transfusion and development of clinical AIDS is 10 and 8 years, respectively [1, 2]. The slow but relentless progression of immunologic dysfunction and clinical pathology characteristic of HIV infection is not due to HIV being an intrinsically slowly growing agent, however, but rather to the nature of viral gene regulation and virus-cell and infected cell-host interactions. Retroviruses such as HIV are complex and unusual parasites. They have evolved unique associations with their cellular hosts, including regulatory events that enable them to establish a persistent infection from which replicationcompetent virus may be induced (rescued) through a variety of pathways. Such chronic infection does not represent true molecular latency, with absent expression of viral RNA transcripts and protein. Latency is here defined more generally as the establishment of a virus in its host for prolonged periods in the absence of symptomatology, followed by lytic or other cytopathic episodes. It involves two essential elements: trans-acting viral gene products and their ds-responsive targets, and immune responses ineffectual in recognizing or clearing virions and virus-infected cells [3]. With respect to AIDS, early in the course of HIV infection absolute numbers of CD4+ T lymphocytes may be within normal limits while many measures of cellular immunity are markedly perturbed [4]. This was initially puzzling as, by the limits of in situ hybridization, ^ in 10,000 circulating or tissue-associated T and B lymphocytes and monocytes was reported to contain HIV nucleic acid [5]. Recent data indicate, however, that much greater numbers of cells may be chronically infected in vivo, persisting as stationary cell intermediates from which HIV may be rescued by a variety of seemingly disparate stimuli. The frequency of infected peripheral CD4+ T lymphocytes in AIDS patients is at least 196