Protein That Destroys HIV Identified As TRIM5a

[tetano]

Protein that destroys HIV identified as TRIM5a. The new discovery of TRIM5a could lead to protein-based treatments that destroys HIV in humans. The first TRIM5a destroys the virus after the first protein latches on to the HIV.

Destroys HIV virus, according to researchers who have identified the key component called TRIM5a. The new discovery would knock out HIV in humans, and could change health care as we know it today. Moreover, it could save lives of those already infected with the virus.

This new discovery could eventually lead to new TRIM5a-based treatments for HIV patients. Edward M. Campbell, PhD, of Loyola University Health System is the senior researcher. Campbell and colleagues have reported their findings in the Sept. 15, 2010 issue of Virology.

Researchers hope to turn TRIM5a into an effective therapeutic agent. However, first they need to identify the components in TRIM5a that enable the protein to destroy viruses. "Scientists have been trying to develop antiviral therapies for only about 75 years" Campbell said. "Evolution has been playing this game for millions of years, and it has identified a point of intervention that we still know very little about." TRIM5a consists of nearly 500 amino acid subunits.

http://www.newsoxy.com/health/protein-that-destroys-hiv-14400.html

 

[Giuseppe]

Re: Protein That Destroys HIV Identified As TRIM5a

TRIM5 Suppresses Cross-Species Transmission of a Primate Immunodeficiency Virus and Selects for Emergence of Resistant Variants in the New Species (PLOS, abstract, edited)


[Source: PLOS, full text: <cite cite="http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1000462?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+plosbiology%2FNewArticles+%28PLoS+Biology%3A+New+Articles%29">PLoS Biology: TRIM5 Suppresses Cross-Species Transmission of a Primate Immunodeficiency Virus and Selects for Emergence of Resistant Variants in the New Species</cite>. Abstract, edited.]

TRIM5 Suppresses Cross-Species Transmission of a Primate Immunodeficiency Virus and Selects for Emergence of Resistant Variants in the New Species

Andrea Kirmaier 1,2, Fan Wu 3, Ruchi M. Newman 4, Laura R. Hall 1, Jennifer S. Morgan 1, Shelby O'Connor 5, Preston A. Marx 6, Mareike Meythaler 2,7, Simoy Goldstein 3, Alicia Buckler-White 3, Amitinder Kaur 7, Vanessa M. Hirsch 3, Welkin E. Johnson 1*

1 New England Primate Research Center, Department of Microbiology and Molecular Genetics, Harvard Medical School, Southborough, Massachusetts, United States of America,
2 Institut f?r Klinische und Molekulare Virologie, Friedrich-Alexander-Universit?t Erlangen-N?rnberg, Germany,
3 Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, United States of America,
4 Genome Sequencing and Analysis Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America,
5 Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin, United States of America,
6 Tulane Regional Primate Research Center, Covington, Louisiana, United States of America,
7 New England Primate Research Center, Division of Immunology, Harvard Medical School, Southborough, Massachusetts, United States of America


Abstract

Simian immunodeficiency viruses of sooty mangabeys (SIVsm) are the source of multiple, successful cross-species transmissions, having given rise to HIV-2 in humans, SIVmac in rhesus macaques, and SIVstm in stump-tailed macaques. Cellular assays and phylogenetic comparisons indirectly support a role for TRIM5α, the product of the TRIM5 gene, in suppressing interspecies transmission and emergence of retroviruses in nature. Here, we investigate the in vivo role of TRIM5 directly, focusing on transmission of primate immunodeficiency viruses between outbred primate hosts. Specifically, we retrospectively analyzed experimental cross-species transmission of SIVsm in two cohorts of rhesus macaques and found a significant effect of TRIM5 genotype on viral replication levels. The effect was especially pronounced in a cohort of animals infected with SIVsmE543-3, where TRIM5 genotype correlated with approximately 100-fold to 1,000-fold differences in viral replication levels. Surprisingly, transmission occurred even in individuals bearing restrictive TRIM5 genotypes, resulting in attenuation of replication rather than an outright block to infection. In cell-culture assays, the same TRIM5 alleles associated with viral suppression in vivo blocked infectivity of two SIVsm strains, but not the macaque-adapted strain SIVmac239. Adaptations appeared in the viral capsid in animals with restrictive TRIM5 genotypes, and similar adaptations coincide with emergence of SIVmac in captive macaques in the 1970s. Thus, host TRIM5 can suppress viral replication in vivo, exerting selective pressure during the initial stages of cross-species transmission.


Author Summary

The human immunodeficiency viruses HIV-1 and HIV-2 originated from cross-species transmission of simian immunodeficiency viruses (SIVs) from chimpanzees (SIVcpz) and sooty mangabeys (SIVsm), respectively. A related virus, SIVmac, causes AIDS-like pathogenesis in rhesus macaques; like HIV-2, SIVmac is the product of a cross-species jump of SIVsm from sooty mangabeys. The primate TRIM5 gene encodes a factor with potent antiviral activity when tested in the laboratory, and TRIM5 proteins are thought to play a role in restricting the movement of viruses between species in nature. In this study, we show that genetic variation in the TRIM5 gene of rhesus macaques heavily influences the outcome of cross-species transmission of SIVsm and that emergence of SIVmac in rhesus macaques in the 1970s required adaptations to circumvent the genetic barrier imposed by the rhesus macaque TRIM5 gene. Our results confirm the hypothesis that TRIM5 can influence the process of cross-species transmission and emergence of viruses related to HIV-1 and HIV-2 and serve as a striking illustration of how host genes can influence virus evolution.


Citation: Kirmaier A, Wu F, Newman RM, Hall LR, Morgan JS, et al. (2010) TRIM5 Suppresses Cross-Species Transmission of a Primate Immunodeficiency Virus and Selects for Emergence of Resistant Variants in the New Species. PLoS Biol 8(8): e1000462. doi:10.1371/journal.pbio.1000462

Academic Editor: Michael Emerman, Fred Hutchinson Cancer Research Center, United States of America

Received: May 4, 2010; Accepted: July 14, 2010; Published: August 24, 2010

This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

Funding: This work was supported by grants from the National Institutes of Health (NIH), including grants AI057039 and AI083118 (WEJ), NIH ARRA award AI077423 (WEJ), AI049809 and AI084810 (A Kaur), and by NIH/NCRR grant RR00168 (NEPRC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Abbreviations: CA, capsid protein; CypA, cyclophilin-A; NTD, N-terminal domain; RF, restriction factor; SIVs, Simian immunodeficiency viruses; SIVmac, Simian immunodeficiency viruses of rhesus macaques; SIVsm, Simian immunodeficiency viruses of sooty mangabeys; SIVstm, Simian immunodeficiency viruses of stump-tailed macaques

* E-mail: wjohnson@hms.harvard.edu
-
-----