Archive for February, 2011

InCROIable…Dorian McIlroy reports

28 February, 2011

The penalty for winning a competition here on ViroBlogy is writing an article for ViroBlogy – 2nd prize would, of course be writing TWO articles.  Mind you, as two-time winner, regular commenter Dorian McIlroy gets to do just that.  He has volunteered to report daily from CROI 2011, the 18th Conference on Retroviruses and Opportunistic Infections in Boston, that’s on right now.  Thanks Dr D!

“So here I am in the snow in Boston at the 18th CROI. The opening talk is from Bryan Cullen (Duke, USA) on viruses and micro RNA, known as miRNA. As readers may know, there are three main functions types of RNA inside cells. Messenger RNA (mRNA) is the intermediate between a sequence of DNA and the protein that the DNA sequence encodes. It carries the message, so to speak, telling the protein synthesis machinery what protein to make.  The two other main types of RNA (tRNA and rRNA) are involved in the translation of the mRNA message into protein.

However, in addition to these common or garden types of RNA, cells also produce very small RNA molecules, that do not code for proteins, and are not directly involved in protein synthesis. So what are they for? Well, we will have to wait till Prof. Cullen tells us. Right now, John Coffin (Tufts, USA) is giving the opening talk. There are about 4000 delegates, all lined up in a big auditorium. As you can imagine, the speaker is a little tiny blob at a lectern way, way up at the front. Fortunately, the
speaker’s head and torso is projected on a big screen at the same time.  The films of all the talks are available on the CROI website (www.retroconference.org), which kind of defeats the purpose of  my writing these blog posts I guess…..[NO!  Ed]

But  on with Bryan Cullen. miRNAs are expressed in all multicellular organisms. There are over 1000 of these miRNAs in humans, and their role is to regulate mRNAs – so in fact they control gene expression. In plants and insects, some miRNAs have anti-viral functions, but this is not the case in mammals. In fact, at least one human virus (HCV) uses a host cell miRNA for its own replication.

In addition, some DNA viruses – mostly herpesviruses – also code for miRNAs. One of these is Epstein-Barr Virus (EBV) which is associated with several cancers. When EBV infects B-lymphocytes from the blood, these cells grow in an uncontrolled way (that is, they become pre-cancerous).   It turns out that only one of the EBV miRNAs (BHRF1-2 if you really want
to know) is involved in turning normal B-cells into pre-cancerous cells.  Dr Cullen then goes on to explain an interesting technique called “PAR-CLIP” that allows you to identify the target genes of a particular miRNA, and gives us a list of the cellular genes targeted by  BHRF1-2.

Take-home message – some oncogenic DNA viruses use miRNAs to manipulate host cell biology, and this is involved in their ability to induce cancer.

This is followed by a harrowing story from Fred Hersch, of his own brush with death due to HIV/AIDS. Fortunately, he survived, due to the extraordinary efforts of the ICU at St Vincent’s hospital in New York, and is now playing piano for us all.

After the musical interlude, Anthony Harries (now at the International Union against TB and kung diseases in Paris) gives an excellent talk (hey – not that the first talk wasn’t excellent too) describing his time as head of HIV/AIDS health care in Malawi. He was there when HIV seroprevalence rose from less than 1% to about 15% in the adult population. For several years in the 1990s and the beginning of the century, no treatment was available to stop people from dying. During that
period, 90% of patients diagnosed with stage 4 AIDS were dead one year later. That began to change, he says, with the world AIDS conference in Durban in 2000, where international efforts to make antiretroviral therapy (ART) available in sub-Saharan Africa began to take shape. He then goes on to explain how ART is implemented in Malawi – and shows how coffin sales in one district have plummeted over the last few years. This is the real clinical success of making ART available – the decade-long wave of deaths has abated.

That was the good news. Now for the bad news. Transmission rates are still high – with an estimated 70 000 new HIV infections in Malawi each year. So the HIV problem has certainly not gone away, it has just been contained.  Secondly, current guidelines for starting ART depend on a HIV+ individual’s CD4+ T-cell count, and if you don’t have the means to determine the CD4 count (of the 400 ART centres in Malawi, only about 50 have the machines to measure CD4 T-cell counts), then you can’t start treating all the people who need it. He ends by making a convincing case for, at the very least, giving ART to all pregnant seropositive women in Malawi (and I guess, in the whole of Africa), with a clear recommendation that they continue on medication indefinitely. The objectives of this approach would be to keep mothers alive and healthy while their children
are growing up, and to ensure that the next generation of children are born HIV-free.

And that’s it for the first day.”

Dorian


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