CD4-dependent and CD4-independent HIV-2: consequences for neutralization

• Published in: AIDS (London) Vol. 17; no. 3; pp. 291 - 300
• Main Authors: THOMAS, Elaine R, SHOTTON, Christine, WEISS, Robin A, CLAPHAM, Paul R, MCKNIGHT, Aine
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 14-02-2003
• Subjects: AIDS/HIV; Antibodies, Monoclonal - metabolism; Antibody Specificity; Biological and medical sciences; CD4 Antigens - immunology; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; HIV Antibodies - immunology; HIV Envelope Protein gp120 - immunology; HIV-2 - immunology; Human viral diseases; Humans; Infectious diseases; Medical sciences; Neutralization Tests; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Immunopathology; virus-cell interaction; HIV-2; Antibody; Pathogenesis; Retroviridae; AIDS; Immune deficiency; Lentivirus; In vitro; Host virus relation; Protein; HIV-2 virus; Infection; Virus; Viral disease; Evolution; antibodies; Human immunodeficiency virus; Virus envelope; envelope proteins; Neutralization
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/00002030-200302140-00002

HIV-2 is less pathogenic than HIV-1. In contrast to HIV-1, many isolates of HIV-2, including primary isolates, can infect cells independently of CD4.
To compare the sensitivity of CD4-dependent and CD4-independent isolates of HIV-2 to antibody-mediated neutralization.
The neutralization sensitivity of CD4-dependent and CD4-independent molecular clones of HIV-2 to a panel of HIV-2-positive serum samples was tested. Monoclonal antibodies to various epitopes across the viral envelope were used to determine whether a specific epitope conferred neutralization sensitivity. Neutralization sensitivity of primary isolates of HIV-2 able to infect in the absence of cellular CD4 was also investigated. Antibody binding to sensitive and resistant envelopes was analysed using enzyme-linked immunosorbent assay and flow cytometry.
CD4-independent ROD B was highly sensitive to neutralization by HIV-2-positive sera compared with the CD4-dependent isolate ROD A. Induction of ROD A to infect CD4-negative cells by soluble CD4 rendered it equally sensitive to antibody neutralization. Similarly, primary X4, R5 or dual-tropic isolates of HIV-2 were significantly more susceptible to neutralization when utilizing a CD4-independent route of infection. Neutralization sensitivity was not epitope specific but several conformation-dependent antibodies accentuated this phenotype. Antibody binding to monomeric or oligomeric envelope did not correlate with neutralization sensitivity.
HIV-2 isolates utilizing a CD4-independent route of infection are more sensitive to antibody-mediated neutralization. Cellular CD4 may protect HIV-2 from neutralization. This sensitivity to neutralization may, in part, explain the lower virus load and slower progression to disease in HIV-2-infected individuals.