Page #30
MA: In the coming winter some portion of the 33 million souls who carry the HIV pathogen will be challenged with:
1. Influenza vaccine or
2. Neuraminidase Inhibitors after being infected with H1N1 or
3. Neuraminidase Inhibitors prophylactically or
4. H1N1 infection
5. Or any combination thereof
This is what we know as fact:
1. Over 100,000,000,000,000,000 human immunodeficiency virus genomes are produced daily on the entire planet. As a consequence, thousands of viral mutants arise by chance every day.
2. The HIV-1 genome, which is about 10,000 nucleotides long, can exist as 10 to the 6,020th power different sequences. To put this number in perspective, there are 10 to the 11th power stars in the Milky Way galaxy and 10 to the 80th power protons in the universe.
3. The enormous variability of HIV is an effective mechanism for evading neutralizing antibody. The sequence variation in one isolate from a single HIV-infected individual sampled a few years after infection is greater than the global variation of an influenza epidemic strain during a flu season .
Q: Well it certainly is a fast changing agent.
MA: It is much more than that. We have known since 1996 that you can enhance infectivity in HIV by neuraminidase treatment. This effect is due to increased binding capacity of the treated virus to the target cells.
But, more importantly, we have known since 2002 thanks to the work of Jiangfeng Sun et al. that virion-associated flu NA has an enhancing effect on HIV-1-mediated syncytium formation and cell-free virus infection.
In the laboratory they showed that treating cells with flu-derived NAs remarkably augmented the initial cell-cell interaction and promoted HIV-1-mediated cytopathic effect (i.e. syncytium formation). And that the desialylation of target cells increased susceptibility of target cells to infection with cell-free HIV-1 particles
I understand that this is very technical, but the short version is that when you subject HIV to neuraminidase you can enhance its syncytium formation and replication.
This is not something you wish to do with a highly mutagenic agent like HIV.
Q: OK, so if we treat HIV with neuraminidase we increase its infectivity. I have that. But what happens when you treat an HIV + person with neuraminidase inhibitors such as Tamiflu.
MA: Yes that is the question is it not? In fairness you can say that we have not seen any huge changes in the virus by Tamiflu treatment - thus far.
However Dr. Chueh Huang is doing ground-breaking work that shows that NA inhibitors could enhance the frequency with which two viruses infect the same cell. This is called "superinfection". When two viruses infect the same cell the oportunity for viral reassortment increases. Thus the enzymatic activity of NA is essential for superinfection exclusion - and to go messing around with this natural roadblock to superinfection and reassortment is playing with fire.
In my personal opinion, we do not have enough information to treat HIV with any agent that targets neuraminidase.
