Open Reading Frame E3-10.9K of Subspecies B1 Human Adenoviruses Encodes a Family of Late Orthologous Proteins That Vary in Their Predicted Structural Features and Subcellular Localization

Frietze, Kathryn M.; Campos, Samuel K.; Kajon, Adriana E.

doi:10.1128/jvi.00512-10

Cited by 8 publications

(19 citation statements)

References 61 publications

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“…Sequencing of the 5’ end of RT-PCR transcripts revealed splicing to the tripartite leader sequence suggesting the gene is expressed from the major late promoter. This is consistent with other E3 proteins previously shown to be expressed at both early and late time points, and when late, found to be spliced to the tripartite leader (Blusch et al, 2002; Frietze et al, 2010; Li and Wold, 2000; Windheim and Burgert, 2002). Northern blot analysis using a probe targeted to the interior of the CR1-γ gene confirmed the kinetics of expression, but also revealed multiple bands increasing from 4 to 48 hours post-infection.…”

Section: Discussionsupporting

confidence: 91%

“…Using PredictProtein, the putative amino acid sequence is predicted to contain a N-terminal signal sequence, a luminal domain, a transmembrane domain, and a cytoplasmic domain consisting of 39 residues. Nine N-glycosylation sites were predicted on the luminal domain, consistent with other glycosylated E3 proteins (Blusch et al, 2002; Frietze et al, 2010; Hawkins and Wold, 1995; Li and Wold, 2000; Windheim and Burgert, 2002). A protein kinase C phosphorylation site, located within the cytoplasmic domain, suggests that this protein may function through PKC to modulate other host proteins.…”

Section: Discussionsupporting

confidence: 75%

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The E3 CR1-gamma gene in human adenoviruses associated with epidemic keratoconjunctivitis

Robinson¹,

Rajaiya²,

Zhou³

et al. 2011

Virus Research

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Human adenovirus species D type 37 (HAdV-D37) is an important etiologic agent of epidemic keratoconjunctivitis. Annotation of the whole genome revealed an open reading frame (ORF) in the E3 transcription unit predicted to encode a 31.6 kDa protein. This ORF, also known as CR1-γ, is predicted to be an integral membrane protein containing N-terminal signal sequence, luminal, transmembrane, and cytoplasmic domains. HAdV-D19 (C), another viral pathogen causing epidemic keratoconjunctivitis, contains an ORF 100% identical to its HAdV-D37 homologue but only 66% identical to other HAdV-D homologues. Kinetics of RNA expression and confirmation of splicing to the adenovirus tripartite leader sequence suggest a role for the protein product of CR1-γin the late stages of the viral replication cycle. Confocal microscopy is consistent with expression in the cytoplasm. Sequence analysis reveals a hypervariable luminal domain and a conserved cytoplasmic domain. The luminal domain is predicted to contain multiple N-glycosylation sites. The cytoplasmic domain contains a putative protein kinase C phosphorylation site and potential YXXϕ and dileucine (LL) motifs suggesting a potential role in modification of host proteins.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 75%

The E3 CR1-gamma gene in human adenoviruses associated with epidemic keratoconjunctivitis

Robinson¹,

Rajaiya²,

Zhou³

et al. 2011

Virus Research

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show abstract

“…Overall, E3 represents one of the most divergent regions of Ads (20,21). Although some E3 proteins of species B, D, and E have been characterized biochemically (3,(22)(23)(24), no immunomodulatory function has been assigned to E3 proteins of Ads other than species C or to species-specific E3 proteins.…”

mentioning

confidence: 99%

A unique secreted adenovirus E3 protein binds to the leukocyte common antigen CD45 and modulates leukocyte functions

Windheim

Southcombe

Kremmer

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Significance Human adenoviruses encode Early region 3 (E3) proteins that manipulate the host immune response to establish an infection or to persist longer. To date, only a few E3 functions from a single adenovirus species (C) have been characterized, all of which act directly on infected cells. Here we describe a secreted E3 protein that is uniquely expressed by species D adenoviruses. This protein targets noninfected leukocytes using a cell surface phosphatase as a receptor. We provide evidence that this interaction suppresses leukocyte activation and effector functions, implying that species D adenoviruses can affect the host distant from the site of infection.

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“…Because of similarities in location in the E3 transcription unit, molecular weight, expression kinetics and predicted structural features, we hypothesized that HAdV-B1 E3-10.9K was a homolog of HAdV-C E3-11.6K/ADP [21,22]. The results of our experiments examining growth, dissemination and cell killing phenotypes of HAdV-3-E3-9K mutants provide evidence that this HAdV-B1-specific E3 protein does not function in an analogous manner to the well-characterized ADP.…”

Section: Discussionmentioning

confidence: 99%

No evidence of a death-like function for species B1 human adenovirus type 3 E3-9K during A549 cell line infection

2012

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BackgroundSubspecies B1 human adenoviruses (HAdV-B1) are prevalent respiratory pathogens. Compared to their species C (HAdV-C) counterparts, relatively little work has been devoted to the characterization of their unique molecular biology. The early region 3 (E3) transcription unit is an interesting target for future efforts because of its species-specific diversity in genetic content among adenoviruses. This diversity is particularly significant for the subset of E3-encoded products that are membrane glycoproteins and may account for the distinct pathobiology of the different human adenovirus species. In order to understand the role of HAdV-B-specific genes in viral pathogenesis, we initiated the characterization of unique E3 genes. As a continuation of our efforts to define the function encoded in the highly polymorphic ORF E3-10.9K and testing the hypothesis that the E3-10.9K protein orthologs with a hydrophobic domain contribute to the efficient release of viral progeny, we generated HAdV-3 mutant viruses unable to express E3-10.9K ortholog E3-9K and examined their ability to grow, disseminate, and egress in cell culture.ResultsNo differences were observed in the kinetics of infected cell death, and virus progeny release or in the plaque size and dissemination phenotypes between cells infected with HAdV-3 E3-9K mutants or the parental virus. The ectopic expression of E3-10.9K orthologs with a hydrophobic domain did not compromise cell viability.ConclusionsOur data show that despite the remarkable similarities with HAdV-C E3-11.6K, HAdV-B1 ORF E3-10.9K does not encode a product with a “death-like” biological activity.

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Open Reading Frame E3-10.9K of Subspecies B1 Human Adenoviruses Encodes a Family of Late Orthologous Proteins That Vary in Their Predicted Structural Features and Subcellular Localization

Cited by 8 publications

References 61 publications

The E3 CR1-gamma gene in human adenoviruses associated with epidemic keratoconjunctivitis

The E3 CR1-gamma gene in human adenoviruses associated with epidemic keratoconjunctivitis

A unique secreted adenovirus E3 protein binds to the leukocyte common antigen CD45 and modulates leukocyte functions

No evidence of a death-like function for species B1 human adenovirus type 3 E3-9K during A549 cell line infection

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