Identification of the envelope V3 loop as a determinant of a CD4-negative neuronal cell tropism for HIV-1.
Some neuronal-derived CD4-negative cells are susceptible to infection with human immunodeficiency virus type 1 (HIV-1). Galactosyl ceramide is an alternate receptor for HIV-1 that appears to bind in vitro to the C2, V3, V4, and V5 regions of gp120. Amino acid variation in the V3 loop of HIV-1 affects cellular tropism in CD4-positive cells, but its effect on CD4-negative cells has not been fully analyzed. Here, we describe the effect of amino acid changes in V3 on the HIV-1 infection of a CD4-negative neuronal cell line, SK-N-MC. The sequence of the V3 domain was found to dramatically alter virus infectivity. Furthermore, a gp120 V3 loop neutralizing monoclonal antibody blocked HIV-1 infection of SK-N-MC cells. This data suggests that V3 may also serve as a primary viral determinant for infectivity of CD4-negative cells.
Trujillo
J R
JR
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Wang
W K
WK
Lee
T H
TH
Essex
M
M
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D015704:CD4 Antigens / Q000032:analysis; D002460:Cell Line; D005699:Galactosylceramides / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry*; D015658:HIV Infections / Q000382:microbiology* / Q000473:pathology; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D008969:Molecular Sequence Data; D009474:Neurons / Q000382:microbiology*; D011991:Receptors, Virus / Q000737:chemistry*
D015704:CD4 Antigens; D005699:Galactosylceramides; D015699:HIV Envelope Protein gp120; D011991:Receptors, Virus