Simian Immunodeficiency Virus Infection of Macaques: End-Stage Disease Is Characterized by Widespread Distribution of Proviral DNA in Tissues

Abstract

Four simian immunodeficiency virus (SIV)-infected macaques in the terminal stages of AIDS were studied. Easily detectable unintegrated proviral DNA was present in nearly every tissue (lymphoid and nonlymphoid) examined. SIV-specific immunohistochemistry revealed that macrophages or macrophage-like cells were the predominant reservoirs for SIV. High burdens of infectious SIV were also characteristic of end-stage disease. At the molecular level, sequence analyses of molecular clones derived directly from tissue demonstrated that SIV, like other RNA viruses, exists as a mixture of closely related genomes. Viruses derived by cocultivation seemed to be selected for their ability to grow in tissue culture and did not represent the wide spectrum of genotypes in tissues. These data indicate that SIV-induced immunodeficiency is a complex, multisystem disease and that SIV replication, in addition to impairing the immune system, may have direct deleterious effects on multiple organ systems.

Novel Adeno-Associated Virus Vector Vaccine Restricts Replication of Simian Immunodeficiency Virus in Macaques

“…For study C, naked DNA as a priming vaccine was also evaluated. At various times after the last vaccine dose, each animal was challenged intravenously with SIVsm/E660, a well-characterized pathogenic SIV (52,55). Immune responses and outcome after challenge for each study are described in the sections that follow.…”

“…The SIV challenge virus used in these studies was SIVsm/ E660 (52,55), which was kindly contributed by Vanessa Hirsch (National Institute of Allergy and Infectious Diseases [NIAID], NIH). The titer of the challenge stock for infectivity in rhesus macaques had been previously determined.…”

Characterization and Implementation of a Diverse Simian Immunodeficiency Virus SIVsm Envelope Panel in the Assessment of Neutralizing Antibody Breadth Elicited in Rhesus Macaques by Multimodal Vaccines Expressing the SIVmac239 Envelope

“…SIVsmE660 serves as a heterologous challenge virus for SIVmac239 immunogens, because, unlike SIVmac251, it is genetically distinct from SIVmac239. However, SIVsmE660 challenge virus stocks arose from in vivo and in vitro passage of virus, leading to the original SIVsmE660 isolate that was derived from the spleen of a terminally ill SIV-infected rhesus macaque by in vitro coculture (126,127). It follows that this in vitro adaptation may have contributed to the unusual neutralization sensitivity of some SIVsmE660 variants, often several orders of magnitude greater than the sensitivity of HIV-1 (17,18) and most other SIVsm variants ( Fig.…”

“…In addition, there is evidence that CD4-independent variants emerge more readily in SIV-infected macaques that progress to disease rapidly, probably because they often fail to develop antibody responses. The rhesus macaque from which SIVsmE660 was derived had transient antibody responses against Env and died 52 days after infection (126). Paradoxically, then, it may be that SIVsm Envs selected for their high virulence in vivo also exhibit greater sensitivity to neutralizing antibodies (45).…”

The polio vaccine: a critical assessment of its arcane history, efficacy, and long-term health-related consequences

“…There are monkey viruses as close to isolates of HIV-2 as HIV-2 isolates are to each other [59:106+]." In May 1991, virus-detection techniques were improved once again, and researchers found SIV DNA in the kidneys of infected monkeys [112]. Minced monkey kidneys were (and still are) used to produce the live polio vaccine [3;59:60].…”