Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual, parenteral, and vertical transmission

• Published in: The Journal of clinical investigation Vol. 94; no. 5; pp. 2060 - 2067
• Main Authors: van't Wout, A B, Kootstra, N A, Mulder-Kampinga, G A, Albrecht-van Lent, N, Scherpbier, H J, Veenstra, J, Boer, K, Coutinho, R A, Miedema, F, Schuitemaker, H
• Format: Journal Article
• Language: English
• Published: United States 01-11-1994
• Subjects: Acquired Immunodeficiency Syndrome - transmission; AIDS/HIV; Amino Acid Sequence; Child; Female; HIV-1 - physiology; Homosexuality; human immunodeficiency virus 1; Humans; Infectious Disease Transmission, Vertical; Macrophages - virology; Male; Molecular Sequence Data
• ISSN: 0021-9738
• DOI: 10.1172/jci117560

Macrophage-tropic, non-syncytium-inducing, HIV-1 variants predominate in the asymptomatic phase of infection and may be responsible for establishing infection in an individual exposed to the mixture of HIV-1 variants. Here, genotypical and phenotypical characteristics of virus populations, present in sexual, parenteral, or vertical donor-recipient pairs, were studied. Sequence analysis of the V3 domain confirmed the presence of a homogeneous virus population in recently infected individuals. Biological HIV-1 clones were further characterized for syncytium inducing capacity on the MT2 cell line and for macrophage tropism as defined by the appearance of proviral DNA upon inoculation of monocyte-derived macrophages. Both sexual and parenteral transmission cases revealed a selective outgrowth in the recipient of the most macrophage-tropic variant(s) present in the donor. In three out of five vertical transmission cases, more than one highly macrophage-tropic virus variant was present in the child shortly after birth, suggestive of transmission of multiple variants. In three primary infection cases, homogeneous virus populations of macrophage-tropic, non-syncytium-inducing variants were present prior to seroconversion, thus excluding humoral immunity as the selective pressure in favour of macrophage-tropic variants. These observations may have important implications for vaccine development.