Munch, J., Janardhan, A., Stolte, N., Stahl-Hennig, C., ten Haaft, P., Heeney, J. L., Swigut, T., Kirchhoff, F., Skowronski, J. (December 2002) T-Cell Receptor : CD3 down-regulation is a selected in vivo function of simian immunodeficiency virus Nef but is not sufficient for effective viral replication in rhesus macaques. Journal of Virology, 76 (23). pp. 12360-12364. ISSN 0022-538X
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Abstract
We investigated the function of severely truncated simian immunodeficiency virus (SIV) Nef proteins (tNef) in vitro and in vivo. These variants emerged in rhesus monkeys infected with SIVmac239 containing a 152-bp deletion in the nef-unique region and have been suggested to enhance SIV virulence (E. T. Sawai, M. S. Hamza, M. Ye, K. E. Shaw, and P. A. Luciw, J. Virol. 74:2038-2045, 2000). We found that the tNef proteins were unable to down-regulate the cell surface expression of major histocompatibility complex class I proteins, CD4, and CD28 and neither stimulated SIV replication nor enhanced virion infectivity. The tNef proteins did efficiently down-regulate T-cell receptor (TCR):CD3 cell surface expression. Nevertheless, the SIVmac239 tnef variants were strongly attenuated in six infected juvenile rhesus macaques. Thus, while the ability of SIV Nef to down-modulate TCR:CD3 cell surface expression apparently confers a selective advantage in vivo, it is insufficient for efficient viral replication in infected macaques. Additional mutations elsewhere in SIVmac239 tnef genomes are required for a virulent phenotype.
| Item Type: | Paper |
|---|---|
| Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells organism description > animal > mammal > primates > monkey organism description > virus |
| CSHL Authors: | |
| Communities: | CSHL labs > Skowronski lab |
| Depositing User: | Matt Covey |
| Date: | December 2002 |
| Date Deposited: | 07 Jan 2014 21:40 |
| Last Modified: | 07 Jan 2014 21:40 |
| PMCID: | PMC136863 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/28752 |
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