Macrophage tropism of simian immunodeficiency virus.

Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

Macrophage tropism of simian immunodeficiency virus.

Diss Abstr Int [B]; 52(7):3413 1992. Unique Identifier : AIDSLINE ICDB/93682471
Banapour B; Univ. of California, Davis

Abstract: Simian immunodeficiency virus (SIV) is the causative agent of a disease in rhesus macaques which closely parallels acquired immunodeficiency syndrome (AIDS) in humans infected with human immunodeficiency virus (HIV). These primate viruses are members of the Lentivirinae subfamily of retroviruses. Lentivirus infection of cells of the immune system, including macrophages, may be an important aspect of viral pathogenesis. Several biological and genetic similarities of SIV and HIV indicate that the SIV/macaque system is a useful animal model for HIV infection of humans and AIDS. The SIV system may be utilized to develop vaccines and antiviral therapies, to study the origin and evolution of primate lentiviruses, and to study mechanisms of viral pathogenesis. To explore the relationship of macrophage tropism and viral pathogenesis, conditions to culture and infect monocyte-derived macrophages from rhesus macaques were established, and the growth properties of two molecular clones of SIV(mac) were studied. Rhesus macrophages supported productive infection of virus derived from the nonpathogenic molecular clone SIV(mac)-1A11. Extensive cytopathology characterized by formation of multinucleated giant cells and release of particle-associated reverse transcriptase activity in culture supernatant were observed. In contrast, virus derived from the pathogenic molecular clone SIV(mac)-239 did not establish productive infection of macrophages, and no cytopathology was observed. Both SIV(mac)-1A11 and SIV(mac)-239 replicated and induced cytopathic effects in cultures of rhesus peripheral blood lymphocytes. These in vitro results, together with reports on the pathogenic potential of these two clones of SIV(mac), suggested that macrophage tropism measured in vitro does not correlate with in vivo virulence. To define the viral determinants of macrophage tropism, reciprocal recombinant viral genomes were constructed between molecular clones of SIV(mac)-239 and SIV(mac)-1A11. Infectious recombinant viruses were rescued by transfection of cloned viral genomes into permissive lymphoid cells. Analysis of recombinant viruses in cultures of macrophages showed that gp130 env of SIV(mac)-1A11 is necessary for entry of virus into macrophages but not sufficient for a complete viral replication cycle in this cell type. Thus, gp130 env and one or more genetic element(s) (exclusive of the long-terminal repeat, transmembrane envelope glycoprotein, second coding exons of tat and rev, and nef) are essential for a complete replication cycle of SIV(mac) in rhesus macrophages. The use of SIV infection of rhesus macaques as an animal model for HIV infection and AIDS offers an opportunity to test the relevance of in vitro properties of viruses to pathogenesis. Macrophage tropism is a feature that has been implicated in AIDS-associated neuropathology. These recombinant viruses have also been experimentally inoculated into rhesus macaques to analyze clinical symptoms and tissue distribution of the virus. Animal studies will be critical for evaluation of the significance of macrophage tropism for pathogenesis in the SIV(mac) system. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD91-37107).

Keywords: Animal Cytopathogenic Effect, Viral Gene Products, env/PHARMACOLOGY Macaca mulatta Macrophages/*MICROBIOLOGY Retroviridae Proteins, Oncogenic/PHARMACOLOGY SIV/DRUG EFFECTS/GENETICS/*PHYSIOLOGY Viral Envelope Proteins/PHYSIOLOGY Virus Replication THESIS
930228
M9320872

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