20.109(F08): Samantha and Jenn's Research Proposal

User:Jennifer Lai User:Samantha Lau

Background: A3G is a protein that shows anti-retroviral activity. It has been extensively studied because of its relevance to HIV and Hepatitis B. A3G exists in two molecular complexes, low molecular mass (lmm) and high molecular mass (hmm). Past studies show that A3G only has antiviral activity in lmm form. It has been suggested that there are two mechanisms of antiretroviral activity. One mechanism involves mutation of the retroviral RNA via deamination, catalyzed by the A3G. The other mechanism proposed leads to delay of infection by reducing efficiency of reverse transcriptase, therefore, affecting viral proliferation. Given the delay of infection, it would be possible to utilize this knowledge when considering future therapeutic developments. We propose to test the latter mechanism by determining which domain (catalytic or pseudo catalytic) interacts with retroviral RNA thereaby affecting reverse transcription.

Ideas: 1)Use Ab to block the catalytic domains and pseudo catalytic domains to determine how each domain affects A3G antiviral activity. To see whether the domain affects reverse transcriptase activity or vif defective HIV infection of nonpermissive cells.(Competitive inhibitor) 2)Mutate catalytic domains to determine each domain's effect on reverse transcriptase activity of viral RNA.

Resources for idea 2: http://www.nature.com/nature/journal/v435/n7038/abs/nature03493.html http://www.retrovirology.com/content/5/1/51 http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WG1-458W9BK-4&_user=501045&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000022659&_version=1&_urlVersion=0&_userid=501045&md5=83ff2c1447195a6e8cecac0e715abcef http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=18604271 http://jvi.asm.org/cgi/reprint/JVI.01658-08v1?view=long&pmid=18987139 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16912295 http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WXR-4NJX42B-3&_user=501045&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000022659&_version=1&_urlVersion=0&_userid=501045&md5=a3c5c36adbef89d19cb79003bf1bfdb8 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17428871 http://www.jbc.org/cgi/content/full/282/44/32065 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17942420 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17670826 http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16971427