Fatal adenovirus infection in a neonate and transmission to health-care workers

Henquell, Cécile; Boeuf, Benoît; Mirand, Audrey; Bacher, Catherine; Traoré, Ousmane; Déchelotte, P.; Labbé, A.; Bailly, Jean‐Luc; Peigue-Lafeuille, H.

doi:10.1016/j.jcv.2009.04.019

Cited by 50 publications

(48 citation statements)

References 16 publications

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“…Genome recombination requires coinfection, which is observed in HAdV infections (8,26,39). Putative recombinants, based on the neutralization epsilon and hemagglutination gamma determinants, are recognized as different prototypes by the community, with additional field strains described based on these two markers (SN and hemagglutination inhibition assays) as case studies in the literature (9,11,12). Recently, these have been thoroughly characterized using high-resolution genomics-based and bioinformatics-based methods in great detail (31,40,41).…”

Section: Discussionmentioning

confidence: 99%

Computational Analysis of Two Species C Human Adenoviruses Provides Evidence of a Novel Virus

et al. 2011

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Human adenovirus C (HAdV-C) species are a common cause of respiratory infections and can occasionally produce severe clinical manifestations. A deeper understanding of the variation and evolution in species HAdV-C is especially important since these viruses, including HAdV-C6, are used as gene delivery vectors for human gene therapy and in other biotechnological applications. Here, the full-genome analysis of the prototype HAdV-C6 and a recently identified virus provisionally termed HAdV-C57 are reported. Although the genomes of all species HAdV-C members are very similar to each other, the E3 region, hexon and fiber (ten proteins total) present a wide range of identity values at the amino acid level. Studies of these viruses in comparison to the other three HAdV-C prototypes (1, 2, and 5) comprise a comprehensive analysis of the diversity and conservation within HAdV-C species. HAdV-C6 contains a recombination event within the constant region of the hexon gene. HAdV-C57 is a recombinant virus with a fiber gene nearly identical to HAdV-C6 and a unique hexon distinguished by its loop 2 motif.

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Section: Discussionmentioning

confidence: 99%

Computational Analysis of Two Species C Human Adenoviruses Provides Evidence of a Novel Virus

et al. 2011

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“…HAdV-D56 (accession no. HM770721) was kindly provided by C. Henquell et al (28). All three virus stocks were grown in A549 cells, purified by CsCl gradient centrifugation, dialyzed, and stored at Ϫ80°C.…”

Section: Methodsmentioning

confidence: 99%

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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“…The general affinity of HAdV species for individual tissues is outlined above, but in particular, members of the largest species, species D, show great variability in their tropisms, with growth in tissues ranging from ocular to gastrointestinal (GI) and respiratory tissues (37,88). The basis of tissue tropism is still not well established.…”

Section: Tissue Tropismmentioning

confidence: 99%

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

2014

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SUMMARY Human adenoviruses (HAdVs) are an important cause of infections in both immunocompetent and immunocompromised individuals, and they continue to provide clinical challenges pertaining to diagnostics and treatment. The growing number of HAdV types identified by genomic analysis, as well as the improved understanding of the sites of viral persistence and reactivation, requires continuous adaptions of diagnostic approaches to facilitate timely detection and monitoring of HAdV infections. In view of the clinical relevance of life-threatening HAdV diseases in the immunocompromised setting, there is an urgent need for highly effective treatment modalities lacking major side effects. The present review summarizes the recent progress in the understanding and management of HAdV infections.

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Fatal adenovirus infection in a neonate and transmission to health-care workers

Cited by 50 publications

References 16 publications

Computational Analysis of Two Species C Human Adenoviruses Provides Evidence of a Novel Virus

Computational Analysis of Two Species C Human Adenoviruses Provides Evidence of a Novel Virus

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

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

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