Monday, May 17, 2010

Two labs, one scoop

My apologies if this post has a mild bitter after-taste.

As most of you know, I've been working really hard on a research project. Unfortunately, mere months before I would have finished, UCSF was published on the same topic...only, its UCSF, meaning they did it better! This is in no way uncommon in the world of scientific research, but still, you can imagine my surprise, shock, and large chip adorning my shoulder.

Overall, I am incredibly proud to be involved in such a field. (this is me trying to see the silver lining) The positive results in this research could very well revolutionize the direction of HIV research from here on out. In the end, its not about who discovered and published what, but who we are helping. The scientific community can be, well, cut-throat more often than not, and this calloused look at the publishing arena totally discredits the entire reason we are (or should be) doing this research. So, I applaud you, UCSF and the amazing research team that finished this project.

When I get my hands on an appropriate link to the published article, or at least an abstract, I will post it here for your reading enjoyment. 

So, its back to the drawing board. But, that also means that I'll have more time to write ridiculous entries until I formulate my new research proposal. Yay!



Given that the research was on HIV, I figure I'll take this post to fill you in on the basics of the virus itself.

I was recently in my local Trader Joe's, enduring an awkward conversation with my checker who was also attempting to ask me out on a date (while wearing a utili-kilt...but that's another story), and he inquired about my involvement in scientific research. I basically told him that I currently work with HIV, and he admitted that, although he was aware of HIV and what it did, he had no idea what the acronym stood for. I told him to guess, and he was only lucky enough to get V.  Close, but no cigar, my kilted friend...


Human Immunodeficiency Virus is quite the amazing and quizzical issue.


Above is a basic illustration of HIV in its collective structures. As you can see, its an enveloped virus, which means it has a lipid based structure that encapsulates the genomic information that actually "creates" the virus. Various envelope proteins stud the lipid envelope and assist with viral entry (but we'll get there in a second). Within that lipid envelope, a viral capsid (or, another fancy encasing) holds the viral RNA (two copies of positive single stranded RNA, or (+) ssRNA). The viral RNA encodes for structural proteins once it has integrated into the host's genome, and gives way to replication.

HIV is a retrovirus, giving it a baltimore classification of VI. Retroviruses are truly amazing, and when they were first discovered , they were completely mind blowing. Retroviruses have the ability to create DNA from RNA with the assistance of Reverse Transcriptase (which is encased in the viral capsid, too). This allows the virus to integrate (with the assistance of Integrase molecules, also included in the viral capsid) into the host (our) DNA. This will reprogram the production information, causing our own cells to produce copies of the virus. This is brilliant, and horrible. In a paper in high school, I related this to a viral trojan horse.

So, before HIV can replicate, it must gain entry into our T-cells. The envelope proteins gp120 and gp41 (meaning "glycoprotein" followed by the molecular weight) interact with our chemokine receptors, and initiate membrane fusion between the viral envelope and the T-cell membrane. This creates a tunnel for the viral capsid to travel to the host's cytoplasm, and uncoating occurs. This leaves the viral RNA and its associated functional molecules to get to work. Reverse Transcriptase creates viral DNA in the host's cytoplasm, and Integrase leads it to the host nucleus, where it is integrated, and spliced into smaller viral genomic copies. These copies encode for the viral proteins and are trafficked out of the nucleus, towards the host's cell membrane, where the new viral RNA will bud. Infection continues, rapidly.

HIV has been very tricky and hard to nail down in terms of treatment and a vaccine, but the more we understand about its life cycle, the more things we are able to target for said treatment. Each time the virus replicates, it has the opportunity to make mistakes, or mutations. If the mutations are severe enough, that particular viral strand will not be able to replicate. But, most minor mutations go unnoticed. These constant mutations are the reason HIV is hard to nail down.

About 6 months ago, a three-year vaccine trial ended in Thailand with an almost 40% success rate. This is incredible, but not anywhere near where we need to be to go into mass production.



I know, this is a lot to swallow all at once, so I'll continue this bit at a later date.
In the mean time, do yourself a favor and take steps to protecting yourself from an incurable virus.

May 18th is HIV Vaccine Awareness Day.