Influenza A viruses Multiplicity reactivation

Influenza viruses are capable of multiple reactivation after inactivation by UV radiation or ionizing radiation.If any of the eight RNA strands that make up the genome contain a lesion that prevents the replication or expression of essential genes, the virus cannot survive when it infects a cell alone (single infection).However, when two or more damaged viruses infect the same cell (multiple infection), viable progeny viruses can be produced as long as each of the eight genome segments is present in at least one undamaged copy.That is, multiple reactivations may occur.After infection, influenza viruses trigger host responses, including increased production of reactive oxygen species, which damage the viral genome.If under natural conditions, viral survival is often challenged by oxidative damage, then multiple reactivation may have a selective advantage as a genome repair process.It has been suggested that multiplex reactivation involving segmented RNA genomes may resemble the earliest evolved form of sexual interaction in the RNA world, which may have preceded the DNA world.

Human influenza virus

"Human influenza viruses" generally refer to those subtypes that circulate widely in humans.H1N1, H1N2, and H3N2 are the only known subtypes of influenza A viruses currently circulating in humans.

Genetic factors that differentiate "human influenza viruses" from "avian influenza viruses" include:

PB2: (RNA polymerase): Amino acid (or residue) position 627 in the PB2 protein encoded by the PB2 RNA gene.Before H5N1, all known avian influenza viruses had a Glu at position 627, and all human influenza viruses had a lysine.HA: (Hemagglutinin): Avian influenza HA binds alpha 2-3 sialic acid receptors, while human influenza HA binds alpha 2-6 sialic acid receptors. Swine influenza viruses are able to bind two types of sialic acid receptors.Human flu symptoms typically include fever, cough, sore throat, muscle aches, conjunctivitis and, in severe cases, difficulty breathing and potentially fatal pneumonia.The severity of the infection depends largely on the state of the infected person's immune system, and whether the victim has previous exposure to the strain and is therefore partially immune.A follow-up study of the effect of statins on influenza virus replication showed that pretreatment of cells with atorvastatin inhibited virus growth in culture.The highly pathogenic H5N1 bird flu that infected humans was far more severe, killing 50% of those infected. In one case, an H5N1-infected boy became comatose quickly after diarrhea, but developed no respiratory or flu-like symptoms.Influenza A virus subtypes that have been confirmed in humans, in order of known human pandemic fatalities, are:

• H1N1 caused the "Spanish flu" of 1918 and the swine flu pandemic of 2009

• H2N2 caused the "Asian flu" in the late 1950s

• H3N2 caused the "Hong Kong flu" in the late 1960s

• The spread of H5N1 in the mid-2000s was considered a global pandemic threat

• H7N9 was responsible for the 2013 epidemic in China and Dr. Michael Gregg, author of How Not to Die, identified H7N9 as the greatest pandemic threat to influenza A viruses

• H7N7 has some zoonotic potential:it rarely causes disease in humans

• H1N2 is currently circulating in pigs and rarely causes disease in humans

• H9N2, H7N2, H7N3, H5N2, H10N7, H10N3 and H5N8.

Evolution

"All influenza A pandemics since and virtually all influenza A cases worldwide (with the exception of human infections with avian influenza viruses such as H5N1 and H7N7) have been caused by descendants of the 1918 virus,These include "drift" H1N1 viruses and recombinant H2N2 and H3N2 viruses.The latter consisted of the key genes of the 1918 virus and were subsequently updated by incorporating the avian influenza gene encoding a new surface protein, making the 1918 virus truly the "horizon of all epidemics" Mother".Using data from the Influenza Genome Sequencing Project, researchers at the National Institutes of Health concluded that the hemagglutinin gene in H3N2 showed no significant excess of the antigenic region most of the time during the ten-year period studied Mutations, while accumulating strains.This results in one of the variants eventually gaining a higher fitness, becoming dominant, and quickly sweeping through the population and eliminating most of the other variants in a short, rapid evolutionary interval.

In the short-term evolution of influenza A viruses, a 2006 study found that random processes were key.In contrast to a constant rate of antigenic change, the evolution of influenza A virus HA antigens appears to be more characterized by intermittent, sporadic jumps.The authors, Nelson et al., performed a phylogenetic analysis of the complete genomes of 413 human influenza A viruses collected throughout New York State.2006 were able to show that genetic diversity, rather than antigenic drift, shapes the short-term evolution of influenza A through random migration and rearrangement.The evolution of these viruses is governed more by genetically distinct strains imported randomly from other geographic locations and less by natural selection.Data collected from 413 genomes demonstrated that within a given season, adaptive evolution occurred infrequently and had small overall effects.Phylogenetic analysis revealed that the different strains arose from newly imported genetic material rather than isolates that had been prevalent in New York in previous seasons.Thus, in the short run, gene flow into and out of the population is more important than natural selection.