APOBEC3G levels predict rates of progression to AIDS

• Main Authors: Wu Hulin, Jin Xia, Smith Harold
• Format: Article
• Language: English
• Published: BMC 2007-03-01
• Series: Retrovirology
• Online Access: http://www.retrovirology.com/content/4/1/20

<p>Abstract</p> <p>Background</p> <p>APOBEC3G (hA3G) is a newly discovered cellular factor of innate immunity that inhibits HIV replication <it>in vitro</it>. Whether hA3G conferrs protection against HIV <it>in vivo </it>is not known. To investigate the possible anti-HIV activity of hA3G <it>in vivo</it>, we examined hA3G mRNA abundance in primary human cells isolated from either HIV-infected or HIV-uninfected individuals, and found that hA3G mRNA levels follow a hierarchical order of long-term nonprogressors>HIV-uninfected>Progressors; and, hA3G mRNA abundance is correlated with surrogates of HIV disease progression: viral load and CD4 count. Another group later confirmed that HIV-infected subjects have lower hA3G mRNA levels than HIV-uninfected controls, but did not find correlations between hA3G mRNA levels and viral load or CD4 count. These conflicing results indicate that a more comprehensive, conclusive investigation of hA3G expression levels in various patient cohorts is urgently needed.</p> <p>Presentation of the hypothesis</p> <p>For exploring whether hA3G abundance might influence HIV disease progression, we have formulated a hypothesis that inlcudes two parts: a) <it>in vivo</it>, the basal hA3G mRNA expression level per PBMC is a constant – with minor physiologic fluctuations – determined by host genetic and epigenetic elements in a healthy individual; and that the basal hA3G mRNA expression levels in a population follow a Normal (or Gaussian) distribution; b) that although HIV infects randomly, it results in more rapid disease progression in those with lower hA3G mRNA levels, and slower disease progression in those with higher hA3G mRNA levels.</p> <p>Testing the hypothesis</p> <p>This hypothesis could be tested by a straighforward set of experiments to compare the distribution of hA3G mRNA levels in HIV-uninfected healthy individuals and that in HIV-infected, antiretroviral therapy-naïve subjects who are at early and late stages of infection.</p> <p>Implication of the hypothesis</p> <p>Testing this hypothesis will have significant implications for biomedical research. a) It will link hA3G to the mechanisms underlying slower disease progression in long-term nonprogressors. And, b) It may help to establiseh a new prognostic marker, the hA3G abundance measurement, for HIV-infected patients.</p>