West African HIV-2-Related Human Retrovirus with Attenuated Cytopathicity

Abstract

Clinical and seroepidemiological studies in West Africa indicate that human immunodeficiency virus type 2 (HIV-2) is widespread and associated with immunodeficiency states of variable degree. In this study, an isolate of HIV-2 from a patient in Senegal was molecularly cloned and characterized. This isolate (HIV-2ST) was shown by hybridization and restriction enzyme analysis to be more related to the prototype HIV-2ROD than to other human or primate retroviruses. Cultures of HIV-2ST showed genotypic polymorphism, and clones of the virus had transmembrane envelope glycoproteins of 30 and 42 kilodaltons. Unlike other immunodeficiency viruses, HIV-2ST did not cause cell death or induce cell fusion in peripheral blood lymphocytes or in any of four CD4+ cell lines tested. Although HIV-2ST entered cells by a CD4-dependent mechanism and replicated actively, cell-free transmission of the virus was retarded at the level of cell entry. These findings suggest that immunodeficiency viruses prevalent in West African populations are members of the HIV-2 virus group and that certain strains of this virus have attenuated virulence.

Low‐cytopathic infectious clone of human immunodeficiency virus type I (HIV‐I)

“…Such a defect would imply that only a small proportion of virus preparation (i.e., nondefective particles) would be able to enter cells at any given time. Higher multiplicity of infection of an input virus should then correlate with increased cytopathicity, but that was not the case with HIV-11s~ [6] or NlT-E described here (not shown). Alternatively, the defect could be at the level of virus expression during some stage after virion penetration.…”

“…Recent reports on noncytopathic HIV-II isolates [6,7] implied a correlation with the generally mild course of immunodeficiency in West African patients infected with this virus [8]. Our low-cytopathic HIV-I/NlT-E clone originated from a patient with lymphadenopathy [ 151, who remains relatively healthy.…”

“…The basis for the observed low cytopathicity of NlT-E virus is unclear. One possibility is a defect at the level of virus entry, as suggested for a noncytopathic HIV-11s~ [6]. Such a defect would imply that only a small proportion of virus preparation (i.e., nondefective particles) would be able to enter cells at any given time.…”

“…Five of the 6 clones could be distinguished by restriction endonuclease mapping, and all but one were biologically active. Thus, like the previously described HIV-I/IIIB and HIV-2s~ isolates [6,17], HIV-I/NIT virus contains multiple different genotypes that are capable of producing infectious progeny virus. Fig.…”

“…As shown for several other HIV-I and HIV-II isolates [6,16,17], HIV-I/NlT virus was found to contain multiple virus genotypes [lo]. A recombinant DNA phage library prepared 258 from HIV-I/NlT-producer cells yielded 21 HIT-I positive clones, 6 of which were analyzed and five of them were found to contain a full-length proviral DNA.…”