Induction of AIDS by simian immunodeficiency virus from an African green monkey: species-specific variation in pathogenicity correlates with the extent of in vivo replication

Abstract

Previous studies suggested that simian immunodeficiency viruses isolated from African green monkeys (SIVagm) are relatively nonpathogenic. The report describes the isolation and biologic and molecular characterization of a pathogenic SIVagm strain derived from a naturally infected African green monkey. This virus induced an AIDS-like syndrome characterized by early viremia, frequent thrombocytopenia, severe lymphoid depletion, opportunistic infections, meningoencephalitis, and death of five of eight macaques within 1 year after infection. An infectious clone derived from this isolate reproduced the immunodeficiency disease in pig-tailed (PT) macaques, providing definitive proof of the etiology of this syndrome. Although the virus was highly pathogenic in PT macaques, no disease was observed in experimentally infected rhesus macaques and African green monkeys despite reproducible infection of the last two species. Whereas infection of PT macaques was associated with a high viral load in plasma, peripheral blood mononuclear cells, and tissues, low-level viremia and infrequent expression in lymph nodes of rhesus macaques and African green monkeys suggest that differences in pathogenicity are associated with the extent of in vivo replication. The availability of a pathogenic molecular clone will provide a useful model for the study of viral and host factors that influence pathogenicity.

Differential pathogenicity of SHIVSF162 P4 infection in pig‐tailed and rhesus macaques

“…Persistent infection and/or AIDS-like disease progression have also been observed in pig-tailed macaques inoculated with primary isolates of HIV-2 [37,43], in contrast to the common observation of transient infection and lack of pathogenicity in HIV-2 infected rhesus macaques [11,16]. Hirsch et al [26] passaged SIVagm in pig-tailed macaques and observed speciesspecific variations in pathogenicity correlating with the extent of in vivo replication. Chen et al [12] observed enhanced infectivity, but no pathogenicity, after serial passages of an R5-tropic subtype C SHIV in pig-tailed macaques.…”

Simian AIDS: an historical perspective

“…healthy carriers [19]. Among these other isolates only the SIV from African green monkeys has, thus far, proven experimentally pathogenic in macaques [23].…”

HIV causes AIDS: Koch's postulates fulfilled

“…At least 12 SIV strains induce AIDS (within one year) when cultured in adapted cell lines and transferred as tissue culture supernatant to simian species (largely Asian macaques). Here, AIDS is defined by the depletion of CD4÷ T lymphocytes and several indicator opportunistic infections, namely, Pneumocystis caHnii pneumonia, Mycobacterium avium, oral candidiasis, meningoencephalitis, and lymphoma [80][81][82]. Two pathogenic SIV strains (SIVMACA239, SIVAGM90) have been molecularly cloned and the molecular clones have been used to induce AIDS in macaques [80][81][82].…”

“…Here, AIDS is defined by the depletion of CD4÷ T lymphocytes and several indicator opportunistic infections, namely, Pneumocystis caHnii pneumonia, Mycobacterium avium, oral candidiasis, meningoencephalitis, and lymphoma [80][81][82]. Two pathogenic SIV strains (SIVMACA239, SIVAGM90) have been molecularly cloned and the molecular clones have been used to induce AIDS in macaques [80][81][82]. Control macaques inoculated with saline, with inactivated SIVMAcA239 or with SIVMACA239 carrying mutations/deletions in the nef gene failed to induce AIDS in the same macaque species [80,83,84].…”