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Evolution of human immunodeficiency virus type 2 coreceptor usage, autologous neutralization, envelope sequence and glycosylation

¹ Department of Virology, Swedish Institute for Infectious Disease Control and Microbiology and Tumorbiology Center, Karolinska Institutet, SE-171 82 Solna, Sweden
² Unit of Virology, Division of Medical Microbiology, Department of Laboratory Medicine, Lund University, SE-223 62 Lund, Sweden
³ Department of Infectious Diseases/Solna, Karolinska University Hospital, Karolinska Institutet, SE-171 76 Stockholm, Sweden
⁴ Department of Infectious Diseases/Huddinge, Karolinska University Hospital, Karolinska Institutet, SE-141 86 Stockholm, Sweden

Correspondence
Jan Albert
Jan.Albert{at}smi.ki.se

To investigate why human immunodeficiency virus type 2 (HIV-2) is less virulent than HIV-1, the evolution of coreceptor usage, autologous neutralization, envelope sequence and glycosylation was studied in sequentially obtained virus isolates and sera from four HIV-2-infected individuals. Neutralization of primary HIV-2 isolates was tested by a cell line-based assay and IgG purified from patients' sera. Significant autologous neutralization was observed for the majority (39 of 54) of the HIV-2 serum–virus combinations tested, indicating that neutralization escape is rare in HIV-2 infection. Furthermore, sera from 18 HIV-2 patients displayed extensive heterologous cross-neutralization when tested against a panel of six primary HIV-2 isolates. This indicates that HIV-2 is intrinsically more sensitive to antibody neutralization than HIV-1. In line with earlier reports, HIV-2 isolates could use several alternative receptors in addition to the major coreceptors CCR5 and CXCR4. Intrapatient evolution from CCR5 use to CXCR4 use was documented for the first time. Furthermore, CXCR4 use was linked to the immunological status of the patients. Thus, all CXCR4-using isolates, except one, were obtained from patients with CD4 counts below 200 cells µl^–1. Sequence analysis revealed an association between coreceptor usage and charge of the V3 loop of the HIV-2 envelope, as well as an association between the rate of disease progression and the glycosylation pattern of the envelope protein. Furthermore, HIV-2 isolates had fewer glycosylation sites in the V3 domain than HIV-1 (two to three versus four to five). It is proposed here that HIV-2 has a more open and accessible V3 domain than HIV-1, due to differences in glycan packing, and that this may explain its broader coreceptor usage and greater sensitivity to neutralizing antibodies.

An amino acid sequence alignment of the V1, V2 and V3 domains of the HIV-2 envelope protein is available as supplementary material in JGV Online.

The GenBank/EMBL/DDBJ accession numbers for the sequences determined in this study are DQ213026–DQ213040.

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