Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual, parenteral, and vertical transmission.
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.
van't Wout
A B
AB
Department of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Kootstra
N A
NA
Mulder-Kampinga
G A
GA
Albrecht-van Lent
N
N
Scherpbier
H J
HJ
Veenstra
J
J
Boer
K
K
Coutinho
R A
RA
Miedema
F
F
Schuitemaker
H
H
D000163:Acquired Immunodeficiency Syndrome / Q000635:transmission*; D000595:Amino Acid Sequence; D002648:Child; D005260:Female; D015497:HIV-1 / Q000502:physiology*; D006716:Homosexuality; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008264:Macrophages / Q000821:virology*; D008297:Male; D008969:Molecular Sequence Data