Genetic Requirement for Hemagglutinin Glycosylation and Its Implications for Influenza A H1N1 Virus Evolution

Kim, Sang Hyun; Lee, I.; Park, S.; Hwang, Miriam; Bae, Jin‐Young; Lee, S.; Heo, Jun; Park, M. S.; García‐Sastre, Adolfo

doi:10.1128/jvi.00373-13

Cited by 48 publications

(50 citation statements)

References 43 publications

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“…The predicted HA protein showed K at residue 147 (H1 numbering) which is associated with the stabilization of the interaction between HA and sialic acid (Kim et al, 2013). No mutation in D222 (Selleri et al, 2013) (H3 numbering) was observed.…”

Section: Resultsmentioning

confidence: 96%

See 1 more Smart Citation

Temporal insight into the natural generation of a new reassortant porcine influenza virus in a swine holding

Chiapponi

Baioni

Luppi

et al. 2014

Veterinary Microbiology

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Section: Resultsmentioning

confidence: 96%

“…Reassortant porcine IAV viruses carrying genome segment from the pandemic H1N1 are reported in many countries i.e. Germany (Starick et al, 2011(Starick et al, , 2012, UK and Hungary (Howard et al, 2011), Korea (Kim et al, 2013) and Italy .…”

Section: Introductionmentioning

confidence: 99%

Temporal insight into the natural generation of a new reassortant porcine influenza virus in a swine holding

Chiapponi

Baioni

Luppi

et al. 2014

Veterinary Microbiology

View full text Add to dashboard Cite

“…It is possible that three adjacent lysine residues, at positions 236, 242, and 247, stabilize the interactions to result in increased virulence. Similar to the crucial lysine fence in the globular head of hemagglutinin, and associated with pandemic influenza A/H1N1 (2009) virus (60,61), our proposed crucial lysine residues are structurally exposed on the outer surface of the fiber knob (data not shown). We therefore speculate that position 240 is a hot spot and a novel interaction site for virus attachment and cell entry.…”

Section: Discussionmentioning

confidence: 94%

Selection Pressure in the Human Adenovirus Fiber Knob Drives Cell Specificity in Epidemic Keratoconjunctivitis

Ismail

Lee

Dyer

et al. 2016

J Virol

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Human adenoviruses (HAdVs) contain seven species (HAdV-A to -G), each associated with specific disease conditions. Among these, HAdV-D includes those viruses associated with epidemic keratoconjunctivitis (EKC), a severe ocular surface infection. The reasons for corneal tropism for some but not all HAdV-Ds are not known. The fiber protein is a major capsid protein; its C-terminal "knob" mediates binding with host cell receptors to facilitate subsequent viral entry. In a comprehensive phylogenetic analysis of HAdV-D capsid genes, fiber knob gene sequences of HAdV-D types associated with EKC formed a unique clade. By proteotyping analysis, EKC virus-associated fiber knobs were uniquely shared. Comparative structural modeling showed no distinct variations in fiber knobs of EKC types but did show variation among HAdV-Ds in a region overlapping with the known CD46 binding site in HAdV-B. We also found signature amino acid positions that distinguish EKC from non-EKC types, and by in vitro studies we showed that corneal epithelial cell tropism can be predicted by the presence of a lysine or alanine at residue 240. This same amino acid residue in EKC viruses shows evidence for positive selection, suggesting that evolutionary pressure enhances fitness in corneal infection, and may be a molecular determinant in EKC pathogenesis. IMPORTANCEViruses adapt various survival strategies to gain entry into target host cells. Human adenovirus (HAdV) types are associated with distinct disease conditions, yet evidence for connections between genotype and cellular tropism is generally lacking. Here, we provide a structural and evolutionary basis for the association between specific genotypes within HAdV species D and epidemic keratoconjunctivitis, a severe ocular surface infection. We find that HAdV-D fiber genes of major EKC pathogens, specifically the fiber knob gene region, share a distinct phylogenetic clade. Deeper analysis of the fiber gene revealed that evolutionary pressure at crucial amino acid sites has a significant impact on its structural conformation, which is likely important in host cell binding and entry. Specific amino acids in hot spot residues provide a link to ocular cell tropism and possibly to corneal pathogenesis. Human adenoviruses (HAdVs) are major causes of respiratory disease, gastroenteritis, and keratoconjunctivitis (1-4). HAdV infections are also a major concern in immunocompromised hosts, with fatality rates as high as 55% (5). There are 72 HAdVs currently genotyped in GenBank, which are classified into seven species (HAdV-A to -G) as determined by whole-genome analysis. The majority (n ϭ 47) belong to HAdV-D, including types 8, 37, 53, 54, 56, and 64 (6-12). Each of these has been associated with epidemic keratoconjunctivitis (EKC), a highly contagious ocular surface infection (13). HAdV-D evolves by homologous recombination within genes encoding the major HAdV capsid proteins (14). For example, type 64 (previously typed as 19a) is a recombinant with types 19, 22, and 37 in the hexon, penton ba...

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“…Indeed, although the HI and NT titers exhibit similar trends, they are not exactly the same. 19 Therefore, we only used the PRNT to compare the difference in the influenza-specific neutralizing antibody titers of HFD and RFD mice. Overall, based on Table 1, these results suggest that the humoral immune response is impaired in vaccinated obese mice.…”

Section: Obese Mice Have An Impaired Humoral Immune Response To Influmentioning

confidence: 99%

Obesity-induced chronic inflammation is associated with the reduced efficacy of influenza vaccine

Park

Shim

Lee

et al. 2014

Human Vaccines & Immunotherapeutics

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Genetic Requirement for Hemagglutinin Glycosylation and Its Implications for Influenza A H1N1 Virus Evolution

Cited by 48 publications

References 43 publications

Temporal insight into the natural generation of a new reassortant porcine influenza virus in a swine holding

Temporal insight into the natural generation of a new reassortant porcine influenza virus in a swine holding

Selection Pressure in the Human Adenovirus Fiber Knob Drives Cell Specificity in Epidemic Keratoconjunctivitis

Obesity-induced chronic inflammation is associated with the reduced efficacy of influenza vaccine

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