Simian immunodeficiency virus infection of macaques: end-stage disease is characterized by widespread distribution of proviral DNA in tissues.

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Simian immunodeficiency virus infection of macaques: end-stage disease is characterized by widespread distribution of proviral DNA in tissues.

Symp Nonhum Primate Models AIDS. 1990 Nov 28-30;8:40 (abstract no. 24). Unique Identifier : AIDSLINE PRIM8/900024
Hirsch VM; Zack PM; Vogel AP; Johnson PR; Department of Microbiology, Georgetown University and Laboratory; of Infectious Diseases, NIAID, NIH, Rockville, Md

Abstract: A key to the development of new therapeutic modalities and vaccine strategies for AIDS is a more thorough understanding of the natural history and pathogenesis of immunosuppressive lentiviral infections in animal model systems. The most relevant model for AIDS currently available is simian immunodeficiency virus (SIV) infection of macaques. Experimental inoculation of SIV from macaques (SIVmac) or sooty mangabeys (SIVsm) into healthy macaques induces an immunodeficiency syndrome that is strikingly similar to AIDS in humans. Thus, the dissection and understanding of SIV pathogenesis in macaques may provide data directly relevant to HIV-1 infection of humans. However, surprisingly little data is available regarding the basic pathogenesis of SIV-induced AIDS at the gross anatomical and molecular levels. We have undertaken studies to characterize SIV infection in terminally-ill macaques. Tissues from four macaques were evaluated by Southern blot, PCR, immunohistochemistry (for SIV antigens), and virus isolation. Our data showed that SIV proviral DNA was routinely detected by Southern blot analyses in nearly all lymphoid and non-lymphoid tissues. Estimations of proviral copy number indicated that a minimum of 1 in 200 cells in lymphoid tissues may contain proviral DNA. These data agreed with estimations obtained by limiting cell dilutions and virus isolations. Detection of SIV antigens by immunohisto-chemistry generally correlated with detection of provirus by Southern blot analysis. The majority of SIV-antigen expressing cells appeared (by morphology) to be macrophages, or macrophage-like cells. We then sought to characterize SIV genomes in tissues. Specifically, we wished to determine the integration state of proviruses and whether SIV exists as a swarm of related proviruses, similar to other RNA viruses. Restriction and Southern blot analyses revealed that the majority (85 to 99%) of SIV proviral DNA in tissues was unintegrated. To examine the genetic composition of these proviruses, PCR clones of regions of the envelope gene were generated from a representative sample. Analysis of these clones revealed that many distinct, but closely related SIV genomes (a swarm) are present in a single tissue. In contrast, only a subset of this swarm was detected among PCR clones derived from a CEMX174 isolate of this same tissue. Therefore, tissue culture isolates are unlikely to represent the spectrum of proviruses in tissue. These data demonstrate that SIV infection of macaques is a complex multisystem disease, and suggest that primary SIV replication in addition to opportunistic infections may contribute to the multisystem dysfunction associated with end-stage AIDS.

Keywords: Animal Antigens, Viral/ANALYSIS Blotting, Southern DNA Replication DNA, Viral/*ANALYSIS Genes, env Macaca Macrophages/IMMUNOLOGY/ULTRASTRUCTURE Polymerase Chain Reaction Proviruses/GENETICS Simian Acquired Immunodeficiency Syndrome/*DIAGNOSIS/GENETICS SIV/*GENETICS/IMMUNOLOGY Virus Replication/GENETICS ABSTRACT
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M9170970

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