Because many different subtypes of the influenza A hemagglutinin and neuraminidase proteins exist, the human immune system is frequently challenged with new antigens.
For example, point mutations in the HA and NA genes can lead to changes in antigenicity that allow a virus to infect people who were either infected or vaccinated with a previously circulating virus. This phenomenon is referred to as antigenic drift. The genome of influenza A viruses consists of eight single-stranded RNA segments, and the viral particle has two major glycoproteins on its surface: hemagglutinin and neuraminidase.
Figure courtesy of M-T. Hsu and P. All rights reserved. These proteins include three RNA polymerases that function together as a complex required by the virus to replicate its RNA genome. Interestingly, these polymerases have been shown to have high error rates due to a lack of proofreading ability, which leads to high mutation rates in replicated viral genomes and therefore rapid rates of viral evolution.
This high rate of mutation and evolution is one source of influenza virus genetic diversity. Still other proteins encoded by the viral genome include membrane proteins M1 and M2 which are needed for nuclear export and several other functions and, of course, HA and NA which play roles in viral attachment and release from host cells, respectively. Due to the segmented nature of the influenza genome, in which coding sequences are located on individual RNA strands, genomes are readily shuffled in host cells that are infected with more than one flu virus.
For example, when a cell is infected with influenza viruses from different species, reassortment can result in progeny viruses that contain genes from strains that normally infect birds and genes from strains that normally infect humans, leading to the creation of new strains that have never been seen in most hosts.
Moreover, because at least 16 different hemagglutinin subtypes and nine different neuraminidase subtypes have been characterized, many different combinations of capsid proteins are possible.
Of these subtypes, three subtypes of hemagglutinin H1, H2, and H3 and two subtypes of neuraminidase N1 and N2 have caused sustained epidemics in the human population. Birds are hosts for all influenza A subtypes and are the reservoir from which new HA subtypes are introduced into humans Palese, Because influenza viruses were not isolated and cultured until the s, it was not possible to study the origin of the Spanish flu pandemic at the time of this virus's outbreak; indeed, the virus was not extensively studied until the last decade of the twentieth century.
Specifically, in , both frozen and formalin-fixed lung tissue from Spanish flu victims was used to extract nucleic acid and sequence the influenza genome Tautenberger et al. The samples were derived from a U. The sequence of the influenza genome proved to be puzzling and did not immediately answer researchers' questions regarding the strain's origin.
In the later flu pandemics that occurred in and , the responsible strains appeared to have arisen through reassortment of avian-derived HA genes into human strains. The HA sequence bears some similarities to those sequences commonly seen among avian strains, but it differs from them much more than the strains responsible for the later pandemics. Indeed, when comparing the HA genes from all three pandemic strains to those from both Eurasian and North American avian species, the HA genes bear the least resemblance.
Furthermore, the later strains display fewer sequence differences overall and resemble Eurasian avian sequences much more closely than they do North American avian sequences Table 1. They also resemble avian sequences more closely than they do any mammalian sequence. Taken together, these data suggest that pigs may have been an intermediate host for the strain, although this remains to be demonstrated.
Recent evidence indicates that many physicians frequently fail to diagnose influenza, or they do not specifically distinguish the flu from other respiratory viruses that can cause similar symptoms. For example, a study appearing in the New England Journal of Medicine concluded that "most influenza infections in children were not diagnosed clinically" Poehling et al. Centers for Disease Control, the researchers involved in this study tracked attending physicians' diagnoses for pediatric inpatients and outpatients reporting flu-like symptoms at several American hospitals.
They also conducted their own independent diagnoses of the patients, including laboratory confirmation of pathogen presence. The investigators reported that only one-third of the hospitalized patients identified as influenza positive by the surveillance team had been tested for flu as part of the care they received.
The remaining patients were given diagnoses of various other conditions, including asthma, pneumonia, or a "nonspecific diagnosis of viral infection," when in fact they were influenza positive. The study authors thus concluded that "surveillance that relies on data from physician-directed testing alone substantially underestimates the influenza burden," reflecting a "lack of recognition of influenza during most visits. Although the basic biology and genetics of influenza viruses are fairly well understood, heading off future pandemics requires a better understanding of past pandemics and the factors that contribute to virulence , as well as a thorough commitment to tracking the viruses that are circulating in the population by way of focused public health efforts.
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Swine Flu Is Evolution in Action | Live Science
Influenza: Old and new threats. Nature Medicine 10 , S82—S87 link to article. Poehling, K. The underrecognized burden of influenza in young children.
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HA 1 and NA genes of influenza B virus isolates were amplified and sequenced. Phylogenetic comparison and genetic diversity analysis were performed using the bioinformation software. The mutation rate of Victoria-like HA 1 gene was 4.
Genetic Variation Among Influenza Viruses
The predominant type of influenza virus isolates in was also influenza B virus after the H1N1 flu pandemic in Zhejiang province. Many differences of HA 1 and NA amino acids existed in the current isolates when compared to previous influenza B strains. Genetic re-assortment and antigenic drift seemed the main evolutionary mechanism on influenza B virus. How does Europe PMC derive its citations network? Protein Interactions. Protein Families.
Nucleotide Sequences. Functional Genomics Experiments.