Impact of Pregnancy on Intra-Host Genetic Diversity of Influenza A Viruses in Hospitalised Women: A Retrospective Cohort Study

Abstract

Characterising dynamics of Influenza A Viruses (IAV) within-host evolution is an active field of research which may lead to a better understanding of viral pathogenesis. Using a pregnant mouse model, a study has recently suggested that immune modulation during pregnancy could promote the emergence of IAV quasispecies with increased virulence. Herein, we assess the clinical relevance of these findings in humans. We studied IAV intra-host diversity (ihD) in pregnant (n = 36) and non-pregnant (n = 23) women hospitalized in Lyon for IAV infection (01/2015–05/2018). Whole IAV genomes present in nasopharyngeal samples were sequenced in duplicate to analyze reproducible intra-host single nucleotide variants (ihSNV). Counts, relative frequencies and locations of ihSNV were used as indicators of ihD. The median ihSNV/kb counts per segment were between 0 and 1.3. There was >81% ihSNV at relative frequencies between 1–5% for H1N1 and >51% for H3N2 IAV. No significant difference was noted between pregnant and non-pregnant women when considering all or only non-synonymous ihSNV. Seven convergent non-synonymous ihSNV were found; none were significantly associated with pregnancy. These results suggest that modulation of the immune system during pregnancy in humans does not impact IAV ihD, in contrast to mice.

Pharmacological inhibition of poly (ADP-ribose) polymerase by olaparib ameliorates influenza-virus-induced pneumonia in mice

“…The highly transmissible human pathogen IAV mainly attacks human respiratory epithelium with its hemagglutinin binding with sialic acid to initiate endocytosis [18]. Severe symptoms after IAV infection are commonly found in the infant, elderly, pregnant, as well as the immunocompromised populations [19][20][21][22]. IAV can cause serious pandemics in a short time, with shocking and heart-wrenching facts in history, e.g., the 1918 Great Influenza killed almost 1/30 of the global population only in 1.5 years.…”

SARS-CoV-2 exhibits intra-host genomic plasticity and low-frequency polymorphic quasispecies

“…These variants, in combination with the genetic profile of the host, can potentially influence the natural history of the infection, the viral phenotype, but also the sensitivity of molecular and serological diagnostics assays [ 19 , 20 ]. In the case of flu epidemics for example, de novo arising mutations and intra-host diversity not only forms intra-host evolution of Influenza A, but also greatly affects the pathogenesis of the virus [ [21] , [22] , [23] ]. Indeed, it is suggested that SARS-CoV-2 genomic variants that emerge from inter- and intra-host evolution might be associated with susceptibility to SARS-CoV-2 infection and the severity of COVID-19 [ 24 ].…”

Correction: Impact of Pregnancy on Intra-Host Genetic Diversity of Influenza A Viruses in Hospitalised Women: A Retrospective Cohort Study. J. Clin. Med. 2020, 9, 1974

“…The authors wish to make the following corrections to this paper [1]. There was an error in Figure 1: dots describing the ihSNVs count for each patient in panels A and B were omitted during figure formatting, thus Figure 1…”