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Vincent Racaniello broadcasts live from ASV

August 8, 2011

ResearchBlogging.org

Social media is rapidly changing the way scientific research and knowledge are spread. Vincent Racaniello recently wrote an interesting post entititled “Live tweeting of the ASV meeting” about live conference blogging in general, and the lack of conference guidelines for such activities. Let me just say here that I’m glad Vincent blogged about ASV, despite worries expressed to him by others. Vincent Racaniello is one of the authors of Principles of Virology, the virology textbook that I, and countless other science students, learned virology from. I think it’s fantastic that I can still learn lots of virology from Vincent just by reading his virology blog once a month. I couldn’t imagine getting ASV updates from a better source. Since I was unable to attend the meeting, I am glad Vincent’s tweets were accessible. Looking through all his ASV tweets (#ASV11), I saw several mentions of immune responses to viruses, summarized below:

The innate immune response to viral infection might be better in the heart

Racaniello did a lot of tweeting from Barbara Sherry’s talk: “The Cardiac Innate Response to Viral Infection”. Much of this information can also be found in her Journal of Proteome Research publication last year. Viruses can infect the heart just like any other part of the body. However, very few cause myocarditis, or inflammation of the heart muscle. According to Sherry, this suggests that “the cardiac antiviral response is uniquely effective”. If so, then we may be able to learn something about what makes a good antiviral immune response from studying this system.

Many different viruses may cause viral myocarditis, or inflammation of the heart muscle during viral infection. Sherry works with reovirus, as there are both myocarditic and non-myocarditic strains of this virus. Using mass spec, she found that Hsp25 phosphorylation was increased in non-myocarditic virus-infected cells, and decreased by myocarditic strains. As Hsp25 is anti-apoptotic, and apoptosis is required reovirus spread, Hsp25 could be limiting viral spread. When Hsp27 is over expressed in myocyte and fibrobast cultures, it protects cells from viral infection. Hsp25/27 are not just induced or phosphorylated during reovirus infection of cardiac myocytes and fibroblasts, but are induced in additional viral infections as well, suggesting that Hsp25/27 may have a broader role in protection against viral infection.

Li, L., Sevinsky, J., Rowland, M., Bundy, J., Stephenson, J., & Sherry, B. (2010). Proteomic Analysis Reveals Virus-Specific Hsp25 Modulation in Cardiac Myocytes Journal of Proteome Research, 9 (5), 2460-2471 DOI: 10.1021/pr901151k

The Influenza PB1-F2 protein suppresses the innate antiviral immune response

Peter Palese gave a talk, “Pandemic influenza viruses: past and future”, where he discussed the role of PB1-F2 in Influenza pandemics and work towards the development of a universal flu vaccine. According to Peter’s research, the Influenza protein PB1-F2 is made by most pandemic strains, and can suppress interferon-stimulated genes in mice by blocking interferon production, thereby reducing innate viral immunity. My flu researching colleague just sent me a bunch of papers on the subject of PB1-F2, so expect to hear more from me about this in the future.

Conenello GM, Tisoncik JR, Rosenzweig E, Varga ZT, Palese P, & Katze MG (2011). A single N66S mutation in the PB1-F2 protein of influenza A virus increases virulence by inhibiting the early interferon response in vivo. Journal of virology, 85 (2), 652-62 PMID: 21084483

Antibodies to the HA stalk of Influenza virus are protective

I read an article about the possibility of a universal flu vaccine in USA Today while I was on vacation. When I read the headline out loud, my mother looked confused. “We already have a flu vaccine,” she said. “Yes, but we have to get a new one every year,” was my response. Wouldn’t it be great if there was a universal flu vaccine that you could get once, and would protect you against all influenza viruses you encounter over the course of your lifetime? According to Francis Collins, director of the NIH, we may be only about 5 years away from having such a vaccine. Collins says this is because scientists have found “parts of the viral coat that don’t change”. The HA stalk is one such part. Currently, annual flu vaccines induce antibodies to the head of hemagglutinin (HA). However, by immunizing with a headless form of HA, you may be able to generate antibodies to the more conserved HA stalk. The Palese group presented their data from one such experiment at ASV. By immunizing mice with a headless form of HA, Palese et al found that sera from immunized mice were more broadly reactive, and immune responses generated by the vaccine are potent enough to be protective, as immunized mice were protected from homologous challenge.

Steel, J., Lowen, A., Wang, T., Yondola, M., Gao, Q., Haye, K., Garcia-Sastre, A., & Palese, P. (2010). Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain mBio, 1 (1) DOI: 10.1128/mBio.00018-10

Immature dengue virus particles become infectious in the presence of anti-prM antibodies

Jolanda Smit spoke on early events in flavivirus infection, and how pre-existing antibodies to dengue virus can affect these events. A more severe from of dengue virus infection, called dengue hemorrhagic fever, has long been proposed to be caused by pre-existing antibodies to dengue virus, which enhance viral uptake via the Fc receptor. Antibodies to the dengue virus protein prM are significantly higher in patients with severe disease, and Smit discovered that immature dengue virus particles are actually infectious in the presence of anti-prM antibodies. She found that anti-E (glycoprotein) antibodies also posses this ability to render immature dengue virus infectious. In summary, the mechanism by which antibody-dependent enhancement results in dengue hemorrhagic fever has been more fully characterized, and we now know that anti-dengue virus antibodies could be enhancing disease by causing normally noninfectious, immature dengue virus particles to become infectious. As furin (protease) activity was found to be essential for this process, furin inhibitors could potentially be used to treat those with the more severe form of disease.

Rodenhuis-Zybert IA, van der Schaar HM, da Silva Voorham JM, van der Ende-Metselaar H, Lei HY, Wilschut J, & Smit JM (2010). Immature dengue virus: a veiled pathogen? PLoS pathogens, 6 (1) PMID: 20062797

CD8 T cells can migrate to the gut, providing resident memory

David Masopust spoke about memory T cell responses in the intestinal mucosa. Effector CD8 T cells may reach the small intestine either by local infection of the gut-associated lymphoid tissue (GALT) or sometimes by migration (from spleen?) after systemic routes of vaccination. A portion of memory T cells stay in the gut after primary infection, to be ready for secondary infection. These T cells contain granzyme, and are poised for rapid response due to their location.

Masopust, D., Choo, D., Vezys, V., Wherry, E., Duraiswamy, J., Akondy, R., Wang, J., Casey, K., Barber, D., Kawamura, K., Fraser, K., Webby, R., Brinkmann, V., Butcher, E., Newell, K., & Ahmed, R. (2010). Dynamic T cell migration program provides resident memory within intestinal epithelium Journal of Experimental Medicine, 207 (3), 553-564 DOI: 10.1084/jem.20090858

Neutralizing antibodies have limited potential to protect from HIV infection

From the TWiV broadcast live at ASV, it seems that Julie Overbaugh is quite pessimistic about the ability of antibodies to ever prevent HIV infection in real life. According to Overbaugh, antibodies can protect in some very controlled systems, like SIV challenge studies using the same exact antigen, but not in several other systems. The system that Julie is using to evaluate the potential of antibodies is mother-to-child transmission of HIV antibodies in breast milk. Theoretically, if these antibodies could protect against infection, then the child should be protected against infection with panel of viruses from the same geographic area. However, this does not appear to be what is happening. When plasma was taken from infants of HIV-infected mothers to measure neutralization against the virus panel, there was no difference in the breadth of neutralizing antibody responses between infants that later became infected vs. those that did not. Remember that getting infected with HIV once does not mean that you can’t get infected with someone else’s HIV later. There is just not a lot of cross-protection, and there may be too much viral diversity for antibodies to protect against HIV in the real world. But maybe not – I still believe that resurfaced stabilized cores or other altered/artifical HIV antigens may have potential for eliciting broader spectrum antibodies.

Lynch JB, Nduati R, Blish CA, Richardson BA, Mabuka JM, Jalalian-Lechak Z, John-Stewart G, & Overbaugh J (2011). The breadth and potency of passively acquired human immunodeficiency virus type 1-specific neutralizing antibodies do not correlate with the risk of infant infection. Journal of virology, 85 (11), 5252-61 PMID: 21411521

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