A chimpanzee-passaged human immunodeficiency virus isolate is cytopathic for chimpanzee cells but does not induce disease

Abstract

The human immunodeficiency virus type 1 (HIV-1) readily infects both humans and chimpanzees, but the pathologic outcomes of infection in these two species differ greatly. In attempts to identify virus-cell interactions that might account for this differential pathogenicity, chimpanzee peripheral blood lymphocytes and bone marrow macrophages were assessed in vitro for their ability to support the replication of several HIV-1 isolates. Although the IIlb, RF, and MN isolates did not readily infect chimpanzee peripheral blood lymphocytes, an isolate of HIV-1 passaged in vivo in chimpanzees not only replicated well in both chimpanzee peripheral blood lymphocytes and bone marrow macrophages but also was cytopathic for chimpanzee CD4+ lymphocytes. Because no evidence of HIV-induced disease has been observed in chimpanzees infected with this isolate, in vitro replication to high titers with concomitant loss of CD4+ cells is not, in this instance, a correlate of pathogenicity. These observations, therefore, indicate that caution must be used when making extrapolations from in vitro data to in vivo pathogenesis. Great apes are the only nonhuman species readily infected with the human immunodeficiency virus type 1 (HIV-1) (1, 3,

The ultrastructure of multinucleate giant cells

“…Furthermore, the envelope glycoprotein of an infectious noncytopathic strain of HIV-2 has been found to be unable to induce syncytium formation . Contrary to this, Watanabe et al (1991) have detected a chimpanzee-passaged HIV-1 isolated which is cytopathic to chimpanzee CD4 ÷ cells in vitro and in vivo, but does not cause development of disease. A differential discrimination between HIV-1 infection and syncytium formation has also been advanced by Lifson et al (1991), based upon the CD4 (81-92) amino acid sequence and its interaction with GP120.…”

Loss of CD4+T Cells in Human Immunodeficiency Virus Type 1-Infected Chimpanzees Is Associated with Increased Lymphocyte Apoptosis

“…Novembre et al (40) associated the enhanced pathogenicity of their HIV-1 JC isolate with a putative acquired ability to induce syncytium formation in chimpanzee PBMC in vitro. However, the original stock of HIV-1 LAI/LAV-1b used to inoculate C-499 replicates efficiently in chimpanzee macrophages, forms syncytia with both human and chimpanzee PBMC, and is cytopathic for chimpanzee CD4 ϩ T cells in vitro (20,50). It is unlikely, therefore, that syncytium formation is responsible for disease induction or is a major mode of CD4 ϩ -T-cell loss in HIV-1 JC -or HIV-1 JC499 -infected chimpanzees.…”

From AIDS to Parasite Infection: Pathogen‐Mediated Subversion of Programmed Cell Death as a Mechanism for Immune Dysregulation

“…Second, neuronal loss is observed in the brain (Everall et al 1991) while neurons, in contrast to 004"^ T cells, are not targets for HIV infection, HIV in the central nervous system being expressed primarily in cells of the macrophage lineage (Koenig et al 1986, Michaels et al 1988; these observations suggest that HIV can cause the death of cells that are uninfected. Finally, chimpanzees, the only primates that can be productively and chronically infected with HIV-1, do not, in contrast to HIV-1-infected humans, develop any AIDS-related disease (Johnson et al 1993), even if infected with HIV-1 isolates that are cytopathic in vitro for chimpanzee CD4'*" T cells (Watanabe et al 1991). More generally, the study of primate models of chronic lentiviral infection with human (HIV) and simian (SIV) immunodeficiency viruses have raised important and paradoxical questions about the pathogenesis of AIDS.…”