Characterization of the Pathogenic KU-SHIV Model of Acquired Immunodeficiency Syndrome in Macaques

Abstract

By animal-to-animal passage in macaques we derived a pathogenic chimeric simian-human immunodeficiency virus (SHIV) that caused CD4+ T cell loss and AIDS in pigtail macaques and used it to inoculate 20 rhesus and pigtail macaques by the intravaginal and intravenous routes. On the basis of the outcome of infection and patterns of CD4+ T cell loss and viral load, disease was classified into four patterns: acute, subacute, chronic, and nonprogressive infection. During the study period, 15 of the 20 animals developed fatal disease, including AIDS, encephalitis, pneumonia, and severe anemia. Opportunistic pathogens identified in these animals included Pneumocystis, cytomegalovirus, Cryptosporidium, Toxoplasma, and Candida. No single parameter by itself predicted outcome, although a combination of low CD4+ T cell counts in blood, high plasma virus levels, and presence of autoantibodies to red blood cells reliably predicted a fatal outcome. Five animals (25%) died within 3 months of inoculation and constituted the group with acute disease, whereas the nine animals (45%) with subacute disease died between 3 and 8 months postinoculation. This 70% mortality within 8 months is significantly shorter than in HIV-1-infected human beings, of whom 70% develop fatal disease a decade after infection. SHIV infection in macaques provides a useful model with which to evaluate antiviral strategies, combining all the advantages of the SIVmac system, yet using a virus bearing the envelope gene of HIV-1.

Envelope Glycoprotein Determinants of Neutralization Resistance in a Simian-Human Immunodeficiency Virus (SHIV-HXBc2P 3.2) Derived by Passage in Monkeys

“…Neutralizing antibodies directed against the more conserved elements of the envelope glycoproteins tend to be low in titer. Furthermore, primary HIV-1 isolates are generally more resistant to antibody-mediated neutralization than TCLA isolates (4,30,74). Neutralizing antibodies bind the monomeric gp120 glycoproteins of primary and TCLA isolates with comparable affinity (23,52,68,74).…”

“…SHIVs can infect macaques and elicit HIV-1-specific neutralizing antibody responses. Some SHIVs have been derived by passage in vivo in monkeys, leading to the generation of virus variants that cause rapid CD4 ϩ T-lymphocyte depletion and AIDS-like illness in rhesus monkeys (29,30,60,71,72). One example is SHIVHXBc2, which was constructed with the env gene from a TCLA HIV-1 isolate, HXBc2 (46).…”

“…SHIV-HXBc2 replicated efficiently in monkey peripheral blood mononuclear cells in tissue culture but replicated inefficiently and was apathogenic in several macaque species (46,47). Serial passage of bone marrow from infected monkeys to naive animals generated SHIV KU-1, which caused profound decreases in CD4 ϩ T lymphocytes in infected monkeys within 3 weeks of infection and, eventually, fatal AIDS-like disease (29,30). Substitution of the env gene from SHIV KU-1 into the SHIV-HXBc2 provirus generated a virus, designated SHIV-HXBc2P 3.2, that exhibited CD4 T-lymphocyte-depleting ability and pathogenicity in rhesus monkeys (5).…”

Bleomycin treatment causes enhancement of virus replication in the lungs of SHIV-infected macaques

“…Simian immunodeficiency virus (SIV) and simian HIV (SHIV) infections in macaques have reproduced the pathogenesis of HIV infection in macaques and have been used as models to explore mechanisms of pathogenesis, treatment strategies, and vaccine development against HIV (4,11,17,20). Pneumonia is a rare complication of the disease in macaques, even in animals that have been rendered severely immunodeficient by the virus.…”

Toxoplasmose: levantamento bibliográfico de 1997 a 2000

“…Joag et al 1997 (26) , encontraram, após inoculação do vírus SHIV em macacos, presença de patógenos oportunistas como: pneumocistis, citomegalovírus, criptosporidium, toxoplasma e cândida.…”