Synthetic peptides from the principal neutralizing domain of human immunodeficiency virus type 1 (HIV-1) enhance HIV-1 infection through a CD4-dependent mechanism.
The principal neutralizing domain (PND) of Human Immunodeficiency Virus type 1 (HIV-1) is mapped to a 24-amino acid sequence located in the hypervariable V3 region of the viral envelope protein. The PND of HIV-1 isolates from infected individuals corresponds mostly to that of the HIV-1 MN strain. We found that a peptide designed from the PND of HIV-1 MN virus greatly enhanced viral infection, while a peptide-derived PND of HTLV-IIIB virus showed at least 10-fold less efficient activity; no such effect was exhibited by the other peptides tested, including one designed from the PND of HIV-1 RF strain. The observed enhancing effect occurred in the early steps of viral infection and was not strain-restricted as both MN- and IIIB-derived peptides increased heterologous virus expression, including that of the RF strain. The MN- and, to a lesser extent, IIIB-derived peptides also increased CD4 expression on the cell membrane and differentially inhibited CD4 down-regulation induced by the phorbol ester TPA and/or by the monosialoganglioside GM1; the peptides showing no viral infection enhancement had no such effects. These findings demonstrate that the viral enhancement observed took place through a CD4-dependent mechanism and suggest that the PND is involved in HIV-1 infection and spread.
De Rossi
A
A
Institute of Oncology, Interuniversity Center for Cancer Research, Padova, Italy.
Pasti
M
M
Mammano
F
F
Panozzo
M
M
Dettin
M
M
Di Bello
C
C
Chieco-Bianchi
L
L
D000595:Amino Acid Sequence; D015704:CD4 Antigens / Q000502:physiology*; D002460:Cell Line; D002472:Cell Transformation, Viral; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects
D015704:CD4 Antigens; D010455:Peptides; D014759:Viral Envelope Proteins; D005677:G(M1) Ganglioside; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate