Blockade of human immunodeficiency virus type 1 expression by Caveolin-1

Manuel Llano, Tara Kelly, Maria Vanegas, Mary Peretz, Timothy E. Peterson, Robert D. Simari, Eric M. Poeschla

Research output: Contribution to journalArticle

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Abstract

Caveolin-1 (Cav-1) is a major protein constituent of caveolae, a type of plasma membrane raft. We observed that coexpression of human Cav-1 with human immunodeficiency virus type 1 (HIV-1) blocked virion production from cells that are ordinarily highly permissive. Further investigation showed that this effect is specific, occurs at low ratios of Cav-1 to HIV-1 DNA, depends on expression of Cav-1 protein, and involves severely impaired expression of HIV-1 proteins. Cav-1 also blocked HIV-2 expression. In contrast, Cav-1 did not inhibit protein expression by a paramyxovirus and did not induce apoptosis or affect cellular morphology, cell viability, or cell cycle progression. Although only small amounts of HIV-1 virions were released from Cav-1- transfected cells, these were fully infectious. Deletion mutagenesis showed that the C-terminal 78 residues were as active as the full-length (178-amino-acid) protein in producing the block. In contrast, the 100 most N-terminal amino acids of Cav-1, which include the previously identified oligomerization and scaffolding domains, were shown to be dispensable. Study of single-amino-acid-exchange mutants of Cav-1 established that palmitoylation was not required. Additional deletion mutants then identified the hydrophobic, membrane- associated domain (residues 101 to 135) as the main determinant. Cellular distribution of wild-type and mutant proteins correlated with ability to block HIV-1 expression. Finally, Cav-2 also blocked HIV-1 expression. These data show that coexpression of caveolins can markedly inhibit expression of HIV proviral DNA and establish that the inhibition is mediated by the hydrophobic, membrane-associated domain.

Original languageEnglish (US)
Pages (from-to)9152-9164
Number of pages13
JournalJournal of Virology
Volume76
Issue number18
DOIs
StatePublished - Sep 2002

Fingerprint

Caveolin 1
Human immunodeficiency virus 1
HIV-1
virion
proteins
mutants
Caveolins
amino acids
Human immunodeficiency virus 2
Respirovirus
Amino Acids
Virion
DNA
mutagenesis
Lipoylation
Human Immunodeficiency Virus Proteins
cell viability
Caveolae
cell cycle
HIV-2

ASJC Scopus subject areas

  • Immunology

Cite this

Llano, M., Kelly, T., Vanegas, M., Peretz, M., Peterson, T. E., Simari, R. D., & Poeschla, E. M. (2002). Blockade of human immunodeficiency virus type 1 expression by Caveolin-1. Journal of Virology, 76(18), 9152-9164. https://doi.org/10.1128/JVI.76.18.9152-9164.2002

Blockade of human immunodeficiency virus type 1 expression by Caveolin-1. / Llano, Manuel; Kelly, Tara; Vanegas, Maria; Peretz, Mary; Peterson, Timothy E.; Simari, Robert D.; Poeschla, Eric M.

In: Journal of Virology, Vol. 76, No. 18, 09.2002, p. 9152-9164.

Research output: Contribution to journalArticle

Llano, M, Kelly, T, Vanegas, M, Peretz, M, Peterson, TE, Simari, RD & Poeschla, EM 2002, 'Blockade of human immunodeficiency virus type 1 expression by Caveolin-1', Journal of Virology, vol. 76, no. 18, pp. 9152-9164. https://doi.org/10.1128/JVI.76.18.9152-9164.2002
Llano M, Kelly T, Vanegas M, Peretz M, Peterson TE, Simari RD et al. Blockade of human immunodeficiency virus type 1 expression by Caveolin-1. Journal of Virology. 2002 Sep;76(18):9152-9164. https://doi.org/10.1128/JVI.76.18.9152-9164.2002
Llano, Manuel ; Kelly, Tara ; Vanegas, Maria ; Peretz, Mary ; Peterson, Timothy E. ; Simari, Robert D. ; Poeschla, Eric M. / Blockade of human immunodeficiency virus type 1 expression by Caveolin-1. In: Journal of Virology. 2002 ; Vol. 76, No. 18. pp. 9152-9164.
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