Posts Tagged ‘influenza transmission’

Flu Virus Transmission

Larry H. Bernstein, MD, FCAP, Curator



Mystery behind flu virus transmission solved

lu virus, influenza virus, soft palate

The epidemiological success of flu viruses relies on successful airborne transmission from person to person. But the viral properties governing the airborne transmission of flu viruses are complex. A new study reveals that the soft palate at the back of the roof of the mouth plays a key role in the flu viruses’ ability to transmit through air. Previous research had shown that airborne transmissibility is dependent on the viral surface hemagluttinin (HA) glycoprotein’s ability to bind to receptors on human respiratory cells. Some viral strains bind better to alfa 2-6 glycan receptors found primarily in humans and other mammals while others are better suited to bind alfa 2-3 glycan receptors found in birds.

In the current study, researchers made 4 mutations in the HA protein of the flu virus which made it better suited to bind the bird receptors than the human receptors. They then used this strain to infect ferrets that are often used as models of human influenza infection. In theory the mutated virus should not have spread but it traveled through the air just as well as the wild type virus strain. Upon sequencing the virus genome, the scientists found that it had undergone a genetic reversion that allowed its HA protein to bind to the bird as well as human receptors. This experiment validated that gain of binding to the human receptor is critical for aerosol transmission. On examining the different parts of the respiratory tract, scientists discovered that viruses that genetically reverted were most abundantly found in the soft palate. The researchers are next trying to figure out how this genetic reversion takes place and why particularly in the soft palate. They hypothesize that the viruses outcompete each other in the soft palate from which they can spread by packaging themselves into mucus droplets produced by cells in the soft palate.

From a pandemic point of view, this study enables the systematic evaluation of highly transmissible viruses. The findings published in Nature will enable scientists better understand how the flu virus develops airborne transmissibility while helping monitor strains that acquire the potential to cause Influenza outbreaks.



The soft palate is an important site of adaptation for transmissible influenza viruses (Sep 2015)

Lakdawala SS1, Jayaraman A2, Halpin RA3, Lamirande EW1, Shih AR1, Stockwell TB3, Lin X3, Simenauer A3, Hanson CT, et al.
Nature. 2015 Oct 1; 526(7571):122-5.    http://dx.doi.org:/10.1038/nature15379. Epub 2015 Sep 23.      http://www.ncbi.nlm.nih.gov/pubmed/26416728

Influenza A viruses pose a major public health threat by causing seasonal epidemics and sporadic pandemics. Their epidemiological success relies on airborne transmission from person to person; however, the viral properties governing airborne transmission of influenza A viruses are complex. Influenza A virus infection is mediated via binding of the viral haemagglutinin (HA) to terminally attached α2,3 or α2,6 sialic acids on cell surface glycoproteins. Human influenza A viruses preferentially bind α2,6-linked sialic acids whereas avian influenza A viruses bind α2,3-linked sialic acids on complex glycans on airway epithelial cells. Historically, influenza A viruses with preferential association with α2,3-linked sialic acids have not been transmitted efficiently by the airborne route in ferrets. Here we observe efficient airborne transmission of a 2009 pandemic H1N1 (H1N1pdm) virus (A/California/07/2009) engineered to preferentially bind α2,3-linked sialic acids. Airborne transmission was associated with rapid selection of virus with a change at a single HA site that conferred binding to long-chain α2,6-linked sialic acids, without loss of α2,3-linked sialic acid binding. The transmissible virus emerged in experimentally infected ferrets within 24 hours after infection and was remarkably enriched in the soft palate, where long-chain α2,6-linked sialic acids predominate on the nasopharyngeal surface. Notably, presence of long-chain α2,6-linked sialic acids is conserved in ferret, pig and human soft palate. Using a loss-of-function approach with this one virus, we demonstrate that the ferret soft palate, a tissue not normally sampled in animal models of influenza, rapidly selects for transmissible influenza A viruses with human receptor (α2,6-linked sialic acids) preference.



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