title: Cytopathicity of human immunodeficiency virus type 2 (HIV-2) in human lymphoid tissue is coreceptor dependent and comparable to that of HIV-1.
abstract: Epidemiological studies have shown that human immunodeficiency virus type 2 (HIV-2) is markedly less pathogenic than HIV-1 in vivo. Individuals infected with HIV-2 exhibit a remarkably slow rate of disease development, and these clinical properties have been attributed presumptively to an "attenuated" phenotype of HIV-2 itself. Here, we investigated the impact of coreceptor usage on the cytopathicity of HIV-2 and compared its pathogenic potential with that of HIV-1 in a unique human lymphoid histoculture model. We found that HIV-2 strains, as well as closely related simian immunodeficiency viruses (SIV), displayed mildly or highly aggressive cytopathic phenotypes depending on their abilities to use the coreceptor CCR5 or CXCR4, respectively. A side-by-side comparison of primary X4 HIV-1 and HIV-2 strains revealed similar, high degrees of cytopathicity induced by both HIV types. Furthermore, we found that HIV-2 coreceptor specificity for CCR5 and CXCR4 determined the target cell population for T-cell depletion in lymphoid tissue. Finally, utilization of the alternate coreceptors BOB and Bonzo did not significantly increase the cytopathic properties of HIV-2. These findings demonstrate that coreceptor preference is a key regulator of target cell specificity and the cytopathic potential of HIV-2, with indistinguishable rules compared with HIV-1. Moreover, HIV-2 strains are not characterized by an intrinsically lower cytopathicity than HIV-1 strains. Therefore, direct cytopathic potential per se does not explain the unique behavior of HIV-2 in people, highlighting that other unknown factors need to be elucidated as the basis for their lesser virulence in vivo.
authors.affiliation: Gladstone Institute of Virology and Immunology, University of California San Francisco, San Francisco, California 94141-91000, USA.
authors.forename: B
authors.initials: B
authors.lastname: Schramm
authors.forename: M L
authors.initials: ML
authors.lastname: Penn
authors.forename: E H
authors.initials: EH
authors.lastname: Palacios
authors.forename: R M
authors.initials: RM
authors.lastname: Grant
authors.forename: F
authors.initials: F
authors.lastname: Kirchhoff
authors.forename: M A
authors.initials: MA
authors.lastname: Goldsmith
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D015497:HIV-1 / Q000472:pathogenicity*; D015498:HIV-2 / Q000472:pathogenicity*; D006801:Humans; D008221:Lymphoid Tissue / Q000821:virology*; D019713:Receptors, CCR5 / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000502:physiology*; D014774:Virulence
chemical_list: D019713:Receptors, CCR5; D019718:Receptors, CXCR4