Role of the Host Genetic Susceptibility to 2009 Pandemic Influenza A H1N1

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.

Shaping neonatal immunization by tuning delivery of synergistic adjuvants via nanocarriers

“…Co-encapsulated formulation ((cGAMP + CL075)-PS) demonstrated inferior Th1 polarization upon vaccination (Figure 5 & Figure S1D-F). A similar trend was observed in rHA-specific CD8 + T cell compartment, where admixture (cGAMP-PS + CL075-PS) triggered IFNγ + release (Figure S2), which has already been proven important in viral clearance upon influenza infection 29–32 . Furthermore, Flublok ® stimulation facilitated the triggering of a population of monofunctional IFNγ + TNF - IL-2 - CD4 + T cells in the co-encapsulated formulation immunized group (Figure S3B).…”

A systematic review and meta-analysis of host genetic factors associated with influenza severity

“…Susceptibility to severe influenza in humans is likely to be polygenic and co-determined by viral characteristics, co-morbidities, and contextual factors [ 27 ]. In addition, the inconsistent evidence of the SNPs can be partially explained by the differences in the genetic background of the populations around the world [ 22 ]. As such, the lack of consistently replicated evidence within diverse populations pinpointing any specific genes in humans, advocates the use of large, hypothesis-free, genome-wide association studies [ 61 ].…”

“…As in many other infectious diseases [ 15 – 17 ], host susceptibility to severe influenza disease is partly determined by specific host genes [ 18 – 20 ] that are involved in viral replication [ 21 ], interferon response [ 15 ], or virus-induced systemic inflammation. Indeed, numerous genes potentially participate in diverse mechanisms against the viral response [ 22 ]. The World Health Organization (WHO) prioritizes the identification of host genetic factors that predispose the host to severe influenza [ 23 ].…”

dbGSRV: A manually curated database of genetic susceptibility to respiratory virus

“…Among host factors, host genetic background attracts more and more attention in these years [ 12 , 13 ]. Adoption, twin and heritability studies provided the first line of evidence [ 14 – 16 ], followed by candidate-gene study, genome-wide association study (GWAS), whole exome sequencing (WES) and whole genome sequencing (WGS) in recent years [ 17 ], revealing that human genetic variants play an important role in susceptibility and severity to infection by altering the expression or function of genes, especially those in genes involved in viral life cycle, host inflammatory and immune response [ 18 – 21 ]. These genetic association studies may help dissect the underling mechanisms of viral pathogenesis and host antiviral defense and may contribute to future clinical risk prediction models, allowing for the stratification of individuals according to risk so that those at high risk would be prioritized for immunization [ 22 ].…”