Bounou S, Dumais N, Tremblay MJ; Conference on Retroviruses and Opportunistic Infections.
Program Abstr 8th Conf Retrovir Oppor Infect Conf Retrovir Oppor Infect 8th 2001 Chic Ill. 2001 Feb 4-8; 8: 81 (abstract no. 131).
Infectious Diseases Res Ctr, CHUQ, Pavillon CHUL, Sainte-Foy, Quebec, Canada.
Background: Previous studies have shown that human immunodeficiency virus type-1 (HIV-1) can incorporate several surface proteins of host origin. Recent findings indicate that host-encoded cell surface constituents retain their functionality when found embedded in the viral envelope. The primary objective of the current study was to define whether interaction between some specific virion-bound host proteins with their natural cognate ligands present on target cells could mediate intracellular signaling cascade(s). Methods: For this purpose, we have generated a whole series of isogenic virus stocks (NL4-3 backbone) bearing or not bearing on their surface foreign CD28, CD54 (ICAM-1), CD80 (B7-1) or CD86 (B7-2) proteins. Results: Our results indicate that incubation of human T lymphoid cells with virions bearing host-derived B7-2 proteins and anti-CD3 antibody can potently activate HIV-1 LTR-driven gene expression. Conclusions: This upregulating effect necessitates the involvement of nuclear factor kappa B (NF-kappaB) and nuclear factor of activated T cells (NFAT) as revealed by the use of vectors coding for dominant-negative versions of both transcription factors (i.e., IkappaBalphaS32A/36A and dnNFAT) and band shift assays. The increase of NF-kappaB activity was abolished when infection with B7-2-bearing HIV-1 particles was performed in the presence of the fusion protein CTLA-4 Ig, suggesting that the interaction between virally embedded B7-2 and CD28 on the target cell is responsible for the observed NF-kappaB induction. The findings presented here provide the first demonstration that signal transduction events can be mediated by host-encoded proteins acquired by HIV-1.
Publication Types:
Keywords:
- Antigens, CD
- Antigens, CD28
- Antigens, CD80
- CD86 protein, human
- HIV Infections
- HIV Long Terminal Repeat
- HIV-1
- Humans
- Intercellular Adhesion Molecule-1
- Membrane Glycoproteins
- NF-kappa B
- T-Lymphocytes
- Transcription Factor RelA
- Transcription Factors
- Transcription, Genetic
- Virion
- genetics
- immunology
Other ID:
UI: 102243912
From Meeting Abstracts