Abstract
Influenza A virus (IAV) is the most common infectious agent in humans, and infects approximately 10–20% of the world’s population, resulting in 3–5 million hospitalizations per year. A scientific literature search was performed using the PubMed database and the Medical Subject Headings (MeSH) “Influenza A H1N1” and “Genetic susceptibility”. Due to the amount of information and evidence about genetic susceptibility generated from the studies carried out in the last influenza A H1N1 pandemic, studies published between January 2009 to May 2020 were considered; 119 papers were found. Several pathways are involved in the host defense against IAV infection (innate immune response, pro-inflammatory cytokines, chemokines, complement activation, and HLA molecules participating in viral antigen presentation). On the other hand, single nucleotide polymorphisms (SNPs) are a type of variation involving the change of a single base pair that can mean that encoded proteins do not carry out their functions properly, allowing higher viral replication and abnormal host response to infection, such as a cytokine storm. Some of the most studied SNPs associated with IAV infection genetic susceptibility are located in the FCGR2A, C1QBP, CD55, and RPAIN genes, affecting host immune responses through abnormal complement activation. Also, SNPs in IFITM3 (which participates in endosomes and lysosomes fusion) represent some of the most critical polymorphisms associated with IAV infection, suggesting an ineffective virus clearance. Regarding inflammatory response genes, single nucleotide variants in IL1B, TNF, LTA IL17A, IL8, IL6, IRAK2, PIK3CG, and HLA complex are associated with altered phenotype in pro-inflammatory molecules, participating in IAV infection and the severest form of the disease.
Highlights
Influenza A virus (IAV), a single-stranded negative-sense RNA virus of the Orthomyxoviridae family, is the most common infectious agent in humans, causing significant morbidity and mortality in infants and the elderly every year [1,2]
A allele enhances the binding of CTCF to the interferon-induced transmembrane protein 3 (IFITM3) promoter, leading to a repressive effect on IFITM3 expression, causing a reduction in protein levels in endosomes and lysosomes. This allele has been associated with IAV infection in three different cohorts; in the FLU09 Cohort, it was reported that there was a higher frequency of homozygosity of risk A allele in patients with severe illness than the mild cases, as well as an increased frequency of the A allele in the Cohort of Genentech challenge study and the PICFlu cohort [46]
Several lines of evidence have determined that the role of host factors in genetic susceptibility to Influenza A Virus infection displays an essential part in the appropriate immune response to the virus, determining the outcome of infection
Summary
Influenza A virus (IAV), a single-stranded negative-sense RNA virus of the Orthomyxoviridae family, is the most common infectious agent in humans, causing significant morbidity and mortality in infants and the elderly every year [1,2]. Influenza infects approximately 10–20% of the world’s population resulting in 3–5 million hospitalizations each year and an estimated 87.1 billion dollars in total annual economic burden in the United States alone [3]. In April 2009, the first influenza A H1N1 cases were registered in Mexico and associated with a surprising number of deaths [5], and it spread rapidly throughout the world [6]. Estimates of the crude hospitalization fatality risk (HFR), defined as the probability of death among H1N1 pdm cases which required hospitalization for medical reasons, ranged from 0% to 52%, with higher estimates from tertiary-care referral hospitals in countries with a lower gross domestic product. In wealthy countries, the estimation was 1%–3% in all settings [7]
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