Day 23: My favorite subject

I wrote about HIV for a number of years and thought I had a decent understanding of the virus. Then I joined Dr. James Hildreth’s lab and my perception of the virus changed radically. James and Dr. Steve Gould received a bit of press in the field for their “Trojan Exosome Hypothesis” a few years back. I am not going to get into the academia/political aspect of the paper, but I will say that prior to reading the paper I thought that the only important proteins in HIV were the virally-encoded proteins. I had no idea that the bulk of the viral envelope was made up of host proteins. With the idea that a virus doesn’t carry anything it doesn’t need, I started studying host protein incorporation. With all I have written and studied about HIV, this is still my favorite HIV topic. I think it’s under appreciated and under studied. There are all of these host molecules on the viral envelope and, from my experience, most people just disregard them. Essentially, HIV is a free-floating immunological synapse.

 

However, there has been an increasing interest in why these are the proteins incorporated into the viral envelope. Within the past year or so there have been a handful of papers showing that HIV preferentially buds from tetraspanin-enriched membranes. Well, there’s a new paper that came out in the Journal of Virology that shows this to be true for another retrovirus, Moloney murine leukemia virus (MoMLV). Segura and colleagues used proteomics to identify proteins incorporated into MoMLV virions. The list was the usual suspects; they look exactly like an exosome. You have tetraspanins (CD9, CD63, CD81), tetraspanin-associated proteins (CD9P-1, beta-1 integrin), rab proteins, MFG-E8, lamps, and cytoskeletal proteins. If you compare the proteins found in this paper with those found in HIV (Chertova J Virol 2005, I think), you get almost a complete overlap.

 

What I find most intriguing about these proteins is that they look exactly like a tetraspanin enriched membrane domain (TEMs). Nobody has figured out what tetraspanins do, although they are highly conserved and found in every cell in the body (as far as I can tell). So, do tetraspanins have some importance in HIV? The jury is still out, but I find it highly unlikely that retroviruses selectively incorporate them for no specific purpose. Hopefully someone will figure this out. I tried my hand at it, but that story is best told over a few beers.

 

M. Linde