Structure and genetics Influenza A viruses

Influenza A viruses are negative-sense, single-stranded, segmented RNA viruses.Several isoforms are labeled according to H value (hemagglutinin type) and N value (neuraminidase type).There are 18 different known H antigens (H1 to H18) and 11 different known N antigens (N1 to N11).H17N10 was isolated from fruit bats in 2012.H18N11 was identified in a Peruvian bat in 2013.Influenza A viruses are structurally very similar to influenza B, C and D viruses.Virus particles (also called virosomes) are 80-120 nm in diameter, so the smallest virus particles have an oval shape.The length of each particle varies widely because influenza is pleomorphic and can exceed tens of microns, producing filamentous virions.Confusion about the nature of influenza virus pleomorphism stems from the fact that laboratory-adapted strains often lose the ability to form filaments and these laboratory-adapted strains were the first to be observed by electron microscopy.Despite these different shapes the virions of all influenza A viruses are similar in composition.They both consist of a viral envelope containing two main types of proteins, wrapped around a central core.

Two large proteins found on the outside of the virus particle are hemagglutinin (HA) and neuraminidase (NA).HA is a protein that mediates the binding of viral particles to target cells and entry of the viral genome into target cells. NA is involved in the release of numerous non-productive attachment sites present in mucus as well as in the release of progeny virions from infected cells.These proteins are often targets of antiviral drugs.Furthermore, they are also antigenic proteins to which host antibodies can bind and trigger an immune response.Influenza A viruses are divided into subtypes based on the types of these two proteins on the surface of the viral envelope.16 HA subtypes and 9 NA subtypes are known, but only H 1, 2 and 3, and N 1 and 2 are common in humans.

The central core of the virion contains the viral genome and other viral proteins that package and protect the genetic material.Unlike the genomes of most organisms, including humans, animals, plants, and bacteria, which consist of double-stranded DNA, the genomes of many viruses consist of a distinct single-stranded nucleic acid, RNA.Unusually for viruses, however, the influenza A virus genome is not a single RNA segment; instead, it consists of segmented negative-sense RNA segments, each containing one or two encoded gene products (proteins) gene.The term negative-sense RNA simply implies that the RNA genome cannot be directly translated into protein; it must first be transcribed into positive-sense RNA before it can be translated into a protein product.The segmented nature of the genome allows the exchange of entire genes between different virus strains

The entire influenza A virus genome is 13,588 bases long and is contained in eight RNA segments that encode at least 10 and as many as 14 proteins, depending on the strain.The relevance or presence of alternative gene products may vary:

Fragment 1 encodes the RNA polymerase subunit (PB2).Fragment 2 encodes the RNA polymerase subunit (PB1) and the cell death-inducing PB1-F2 protein by using a different reading frame from the same RNA fragment.Segment 3 encodes the RNA polymerase subunit (PA) and the PA-X protein, which plays a role in host transcriptional shutdown.Segment 4 codes for HA (hemagglutinin).About 500 hemagglutinin molecules are required to make one virus particle. HA determines the extent and severity of viral infection in a host organism.Segment 5 codes for NP, a nucleoprotein.Segment 6 codes for NA (neuraminidase).About 100 molecules of neuraminidase are required to make one virus particle.Fragment 7 encodes two matrix proteins (M1 and M2) by using different reading frames from the same RNA fragment. About 3,000 matrix protein molecules are required to make one virus particle.The RNA segments of the viral genome have complementary base sequences at the ends that allow them to bind to each other through hydrogen bonds.Transcription of the viral (-) sense genome (vRNA) proceeds only after the binding of the PB2 protein to the host capped RNA, allowing the PA subunit to cleave a few nucleotides after capping.This host-derived cap and accompanying nucleotide serves as a primer for the initiation of viral transcription.Transcription proceeds along the vRNA until it reaches a stretch of several uracil bases, which begins to "stutter," whereby the nascent viral mRNA is polyadenylated, producing a mature transcript for nuclear export and translation by the host machinery.