Tag Archives: M protein

Another Reason Not to Sleep with Swine. Cases of Novel Swine Influenza On the Rise. Triple reassortment influenza A(H3N2) viruses of swine origin with the Pandemic H1N1 virus

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On August 3, 2012, Robert Lowes reported in Medscape News information from the center of Disease Control (CDC) regarding the number of people infected with the novel swine influenza A(H3N2)v  virus.— There have been  29 afflicted with the virus, with 12 new cases reported this week.

It appears that the disease was transmitted by either direct or indirect contact with pigs infected with the swine influenza virus. Most of these were children as adults may have a preexistent immunity. Of the 12 swine influenza cases from this week, 10 were patients who had been exposed to pigs at a county fair in Butler County, Ohio. Another patient was from Hawaii that worked with pigs. The CDC has identified a few cases of human-to-human transmission, and the agency is closely monitoring the virus to see whether it mutates into a version more easily spread among humans in lieu of its similarity to theM2 protein of the pandemic H1N1 influenza virus.

The viral M2 matrix protein (light blue) is responsible for entry of the viral ssRNA into the cytoplasm upon infection.

“We want to understand why we’re seeing more cases than we have in the past,” said Dr. Bresee from the CDC. Possible explanations include a change in the virus’ genetic makeup, more human interaction with sick pigs during summer county fairs, or an increased effort to look for this novel virus.

“We expect that additional cases will be identified,” he added. “We also expect some of the cases might be severe.” The symptoms are similar to the seasonal virus, making the diagnosis difficult.

The swine influenza virus is designated A(H3N2)v, with the “v” standing for variant. The variance is in the “M” gene from the pandemic 2009 influenza A(H1N1) virus which codes for matrix proteins in the viral shell.  The pandemic H1N1 virus has found its way into the nation’s pig herds, leading to the alteration of the A(H3N2) virus that circulates among these animals. The concern is that that by acquiring the M gene from the 2009 H1N1 virus, the H3N2v viruses may be more transmissible from pigs to people and from person-to-person. Using phylogenetic analysis, Nelson in June, 2012 reported it appears the pM (pandemic matrix) gene segment reassorted with multiple lineages of the H1 virus. Additionally, the N2 segment of all H3N2v viruses isolated from humans is derived from a genetically distinct N2 swine that was acquired by reassortment with seasonal human H3N2 viruses in 2001-2002, rather than from the N2 that is associated with the 1998 H3N2 swine lineage. This is the reason for the concern for a pandemic threat with this virus. So far, in vivo testing has detected no increased virulence in A(H3N2)v or rH3N2p viruses.

At least we still have access to the influenza vaccine. That should keep us protected, right? Think again. There is a general misconception about currently available vaccines, the benefits of which, Michael Osterholm from the Center for infectious Disease Research and Policy at the University of Minnesota has stated, have been grossly oversold. “They’re not nearly as effective as we’ve told the public they are,” he says, and he backs that claim with the findings of a meta-analysis he and colleagues conducted last year. The seasonal vaccine was effective in only 59% of patients age 18-65 years. The swine influenza A(H3N2)v virus is also different enough from the prior human H3N2 virus  to make it impervious to the seasonal vaccine requiring another vaccine to be developed before the next pandemic.

Since 2000, another concern is that the influenza A virus has shown a substantial increase in amantadine-resistant strains, most of which have a substitution at amino acid position 31 in the M2 gene. These drugs inhibit the M2 matrix protein needed to get viral ssRNA into the cytoplasm. They work against influenza A strains only, and resistance to the drugs evolves quickly. As a consequence, by the 2009-2010 flu seasons, virtually all strains of both H3N2 and H1N1 had developed resistance.

 

References:

  1. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis . Osterholm MT, Kelley NS, Sommer A, Belongia . Lancet Infect Dis. 2012 Jan;12(1):36-44. Epub 2011 Oct 25
  2. Pathogenicity and transmission in pigs of the novel A(H3N2)v influenza virus isolated from humans and characterization of swine H3N2 viruses isolated in 2010-2011. Kitikoon P, Vincent AL, Gauger PC, Schlink SN, Bayles DO, Gramer MR, Darnell D, Webby RJ, Lager KM, Swenson SL, Klimov A.  J Virol. 2012 Jun;86(12):6804-14. Epub 2012 Apr 4
  3. Evolution of Novel Reassortant A/H3N2 Influenza Viruses in North American Swine and Humans, 2009-2011. Nelson MI, Vincent AL, Kitikoon P, Holmes EC, Gramer MR. J Virol. 2012 Aug;86(16):8872-8. Epub 2012 Jun 13
  4. Cases of Novel Swine Influenza Surging. Lowes, Robert. Medscape News, August 3, 2012
  5. Center for Disease Control. http://www.cdc.gov/flu/swineflu/influenza-variant-viruses-h3n2v.htm)