Genomic characterization of human adenovirus type 4 strains isolated worldwide since 1953 identifies two separable phylogroups evolving at different rates from their most recent common ancestor

González, Gabriel; Bair, Camden R.; Lamson, Daryl M.; Watanabe, Hidemi; Pantó, Laura; Carr, Michael J.; Kajon, Adriana E.

doi:10.1016/j.virol.2019.08.028

Cited by 13 publications

(19 citation statements)

References 84 publications

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“…The two PGs differ significantly in their G + C content and apparent evolutionary rates, and as we recently reported, they also exhibit marked sequence differences in coding regions including but not limited to E1A, E1B, E3, L3, and L4 (14).…”

Section: Introductionsupporting

confidence: 74%

“…sequence analysis and proteotyping of a panel of 47 HAdV-E4 whole genome sequences representing strains enabled us to demonstrate additional differences between the two major phylogroups (PG) of HAdV-E4 described by Gonzalez et al (14), and also among the examined genomic variants clustering within each of the two evolutionary lineages.…”

Section: Discussionmentioning

confidence: 75%

“…view of the magnitude of genetic diversity for this medically important type, confirmed the early groupings of related genomic variants, and identified two major evolutionary lineages designated phylogroups (PG) I, and II (14). PG I and PG II comprise the prototype-like and non-prototype-like genomic variants, respectively.…”

Section: Introductionmentioning

confidence: 62%

“…In this study, we expand our original analysis of intra-and inter-PG genetic variability (14) and use a panel of viruses representative of the spectrum of genetic diversity described for HAdV-E4 to examine the magnitude of inter-and intra-PG phenotypic diversity using an array of cell-based assays and a cotton rat model of HAdV respiratory infection.…”

Section: Introductionmentioning

confidence: 99%

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Human Adenovirus Type 4 Comprises Two Major Phylogroups With Distinct Replicative Fitness and Virulence Phenotypes

Bair

Zhang

González

et al. 2020

Preprint

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Human adenovirus type 4 (HAdV-E4) is the only type (and serotype) classified within species Human mastadenovirus E that has been isolated from a human host to the present. Recent phylogenetic analysis of whole genome sequences of strains representing the spectrum of intratypic genetic diversity described to date identified two major evolutionary lineages designated phylogroups (PG) I, and II, and validated the early clustering of HAdV-E4 genomic variants into two major groups by low resolution restriction fragment length polymorphism analysis. In this study we expanded our original analysis of intra- and inter-PG genetic variability, and used a panel of viruses representative of the spectrum of genetic diversity described for HAdV-E4 to examine the magnitude of inter- and intra-PG phenotypic diversity using an array of cell-based assays and a cotton rat model of HAdV respiratory infection. Our proteotyping of HAdV-E strains using concatenated protein sequences in selected coding regions including E1A, E1B-19K and −55K, DNA polymerase, L4-100K, various E3 proteins, and E4-34K confirmed that the two clades encode distinct variants/proteotypes at most of these loci. Our in vitro and in vivo studies demonstrated that PG I and PG II differ in their growth, spread, and cell killing phenotypes in cell culture and in their pulmonary pathogenic phenotypes. Surprisingly, the differences in replicative fitness documented in vitro between PGs did not correlate with the differences in virulence observed in the cotton rat model. This body of work is the first reporting phenotypic correlates of naturally occurring intratypic genetic variability for HAdV-E4.IMPORTANCEHuman adenovirus type 4 (HAdV-E4) is a prevalent causative agent of acute respiratory illness of variable severity and of conjunctivitis and comprises two major phylogroups that carry distinct coding variations in proteins involved in viral replication and modulation of host responses to infection. Our data show that PG I and PG II are intrinsically different regarding their ability to grow and spread in culture and to cause pulmonary disease in cotton rats.This is the first report of phenotypic divergence among naturally occurring known genetic variants of a HAdV type of medical importance. This research reveals readily detectable phenotypic differences between strains representing phylogroups I and II, and it introduces a unique experimental system for the elucidation of the genetic basis of adenovirus fitness and virulence and thus for increasing our understanding of the implications of intratypic genetic diversity in the presentation and course of HAdV-E4-associated disease.

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Section: Introductionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

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Human Adenovirus Type 4 Comprises Two Major Phylogroups With Distinct Replicative Fitness and Virulence Phenotypes

Bair

Zhang

González

et al. 2020

Preprint

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“…Natural recombination, and its primacy for adenovirus evolution, is recognized mainly in mastadenoviruses, with extensive documentation in certain HAdV species [53][54][55][56][57][58][59]. Occasional discoveries are also reported across other species of the genus, e.g., porcine, canine, and bat AdV [60][61][62].…”

Section: Discussionmentioning

confidence: 99%

Fowl Adenovirus (FAdV) Recombination with Intertypic Crossovers in Genomes of FAdV-D and FAdV-E, Displaying Hybrid Serological Phenotypes

Schachner

González

Endler

et al. 2019

Viruses

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After analyzing 27 new genomes from fowl adenovirus (FAdV) field isolates and so-far unsequenced prototypes, we report the first evidence for recombination in FAdVs. Recombination was confined to species FAdV-D and FAdV-E, accommodating the largest number of, and the intraspecies-wise most differentiated, types. The majority of detected events occurred in FAdV-E, involving segments with parental origin of all constitutive types. Together with the diversity of breakpoints, this suggests widespread recombination in this species. With possible constraints through species-specific genes and diversification patterns, the recombinogenic potential of FAdVs attains particular interest for inclusion body hepatitis (IBH), an important disease in chickens, caused by types from the recombination-prone species. Autonomously evolving, recombinant segments were associated with major sites under positive selection, among them the capsid protein hexon and fiber genes, the right-terminal ORFs 19, 25, and the ORF20/20A family. The observed mosaicism in genes indicated as targets of adaptive pressures points toward an immune evasion strategy. Intertypic hexon/fiber-recombinants demonstrated hybrid neutralization profiles, retrospectively explaining reported controversies on reference strains B3-A, T8-A, and X11-A. Furthermore, cross-neutralization supported sequence-based evidence for interdomain recombination in fiber and contributed to a tentatively new type. Overall, our findings challenge the purported uniformity of types responsible for IBH, urging more complete identification strategies for FAdVs. Finally, important consequences arise for in vivo studies investigating cross-protection against IBH.

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Adenoviruses

Heim,

Kajon

2023

ClinMicroNow

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In 1953, Rowe and colleagues described an “adenoid degeneration agent” that induced spontaneous deterioration of tissue cultures prepared from adenoids of children. In the mid1960s, human adenoviruses (HAdV) were found to cause tumors in rodents, prompting studies that revealed fundamental processes of molecular biology but failed to link the virus convincingly to human cancer. HAdV belong to the Adenoviridae family, Mastadenovirus genus. Adenoviruses are large, nonenveloped, icosahedral viruses 70 to 90 nm in diameter. Adenovirus infections can be epidemic, endemic, or sporadic, with the pattern of circulation, specific syndrome, and severity varying by type, population, and route of exposure. Adenovirus‐associated gastroenteritis is caused primarily by types 40 and 41 of species HAdV‐F, which are also known as the “enteric adenoviruses.”

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Genomic characterization of human adenovirus type 4 strains isolated worldwide since 1953 identifies two separable phylogroups evolving at different rates from their most recent common ancestor

Cited by 13 publications

References 84 publications

Human Adenovirus Type 4 Comprises Two Major Phylogroups With Distinct Replicative Fitness and Virulence Phenotypes

Human Adenovirus Type 4 Comprises Two Major Phylogroups With Distinct Replicative Fitness and Virulence Phenotypes

Fowl Adenovirus (FAdV) Recombination with Intertypic Crossovers in Genomes of FAdV-D and FAdV-E, Displaying Hybrid Serological Phenotypes

Adenoviruses

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