Blocking of feline immunodeficiency virus infection by a monoclonal antibody to CD9 is via inhibition of virus release rather than interference with receptor binding.
A monoclonal antibody, MAb vpg15, inhibits feline immunodeficiency virus (FIV) infection in tissue culture. The antibody is directed to a determinant of the feline cell surface marker, CD9, implying that CD9 may serve as a viral receptor or coreceptor in this system. In cells expressing CD9, MAb vpg15 markedly delayed acute virus infection in terms of reverse transcriptase activity detected in cell culture supernatants. This effect was evident if the antibody was added before, immediately after, or 24 h after virus infection. Binding experiments showed that MAb vpg15 did not block virus binding to the cells. PCR analyses at various intervals postinfection also indicated that MAb vpg15 did not block virus uptake, reverse transcription of viral RNA, or integration into host cell DNA. Multiply spliced mRNAs were detected up to 24 h postinfection in both control and MAb vpg15-treated cells. However, viral mRNAs were markedly diminished in MAb vpg15-treated cells after this time, consistent with a failure of the FIV infection to spread in the cell culture. Treatment of chronically infected cells with MAb vpg15 also caused a sharp diminution in viral particle production, while viral mRNA levels were the same in both untreated and MAb-treated infected cells. Analyses of intracellular and extracellular levels of virus-associated antigens showed an enhanced accumulation of intracellular p24. These findings are consistent with the interpretation that MAb vpg15 acts at a posttranscriptional stage by interfering with the assembly and/or release of virus from the cell.
de Parseval
A
A
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Lerner
D L
DL
Borrow
P
P
Willett
B J
BJ
Elder
J H
JH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000502:physiology*; D002415:Cats; D002460:Cell Line; D016089:Immunodeficiency Virus, Feline / Q000502:physiology*; D008562:Membrane Glycoproteins; D012367:RNA, Viral / Q000032:analysis; D011991:Receptors, Virus / Q000502:physiology*; D060245:Tetraspanin 29; D014158:Transcription, Genetic
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D011991:Receptors, Virus; D060245:Tetraspanin 29