Latent Species C Adenoviruses in Human Tonsil Tissues

Garnett, C. T.; Talekar, G; Mahr, Jeffrey A.; Huang, Wen-Chin; Zhang, Y; Ornelles, David A.; Gooding, Linda R.

doi:10.1128/jvi.02392-08

Cited by 183 publications

(226 citation statements)

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“…We found that the vast majority of adenovirus DNA in tonsil and adenoids is quiescent and preferentially localized in the Tlymphocyte population (12). More recently, we reported that while only a small minority of samples from tonsil donors contain replicating virus (Ͻ15%), most tissue samples (85%) could be stimulated in vitro to activate virus gene expression and replication (13). Together, these findings reveal infection by species C adenoviruses as a two-step process of acute replication in epithelial cells of the nasopharyngeal mucosa, followed by latent infection of lymphocytes in mucosa-associated lymphoid tissues.…”

mentioning

confidence: 89%

“…In naturally infected tonsil lymphocyte populations, the frequency of adenovirus-bearing cells is very low, on the order of 1 cell in 10 4 to 10 5 (13). As an initial step in developing a picture of adenovirus infections in lymphocytes, a number of groups have reported success at infecting human lymphocyte cell lines with species C adenoviruses, and most infections appeared to be nonlytic (5,17,19,20,33), at least over the short term.…”

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confidence: 99%

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Modeling Adenovirus Latency in Human Lymphocyte Cell Lines

Zhang

Huang

Ornelles

et al. 2010

J Virol

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mentioning

confidence: 89%

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confidence: 99%

Modeling Adenovirus Latency in Human Lymphocyte Cell Lines

Zhang

Huang

Ornelles

et al. 2010

J Virol

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“…More than 50 different Ad serotypes have been distinguished, which are classified in six different species (2). In a considerable proportion of patients, Ads persist for a variable length of time after primary infection and may become latent (3,4), with members of species C (e.g., Ad2 or Ad5) being most often detected (3). Their successful propagation in vivo is facilitated by multiple strategies to evade the host immune response (1,5,6).…”

mentioning

confidence: 99%

Conserved Amino Acids within the Adenovirus 2 E3/19K Protein Differentially Affect Downregulation of MHC Class I and MICA/B Proteins

Sester

Koebernick

Owen

et al. 2009

The Journal of Immunology

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Successful establishment and persistence of adenovirus (Ad) infections are facilitated by immunosubversive functions encoded in the early transcription unit 3 (E3). The E3/19K protein has a dual role, preventing cell surface transport of MHC class I/HLA class I (MHC-I/HLA-I) Ags and the MHC-I–like molecules (MHC-I chain-related chain A and B [MICA/B]), thereby inhibiting both recognition by CD8 T cells and NK cells. Although some crucial functional elements in E3/19K have been identified, a systematic analysis of the functional importance of individual amino acids is missing. We now have substituted alanine for each of 21 aas in the luminal domain of Ad2 E3/19K conserved among Ads and investigated the effects on HLA-I downregulation by coimmunoprecipitation, pulse-chase analysis, and/or flow cytometry. Potential structural alterations were monitored using conformation-dependent E3/19K-specific mAbs. The results revealed that only a small number of mutations abrogated HLA-I complex formation (e.g., substitutions W52, M87, and W96). Mutants M87 and W96 were particularly interesting as they exhibited only minimal structural changes suggesting that these amino acids make direct contacts with HLA-I. The considerable number of substitutions with little functional defects implied that E3/19K may have additional cellular target molecules. Indeed, when assessing MICA/B cell-surface expression we found that mutation of T14 and M82 selectively compromised MICA/B downregulation with essentially no effect on HLA-I modulation. In general, downregulation of HLA-I was more severely affected than that of MICA/B; for example, substitutions W52, M87, and W96 essentially abrogated HLA-I modulation while largely retaining the ability to sequester MICA/B. Thus, distinct conserved amino acids seem preferentially important for a particular functional activity of E3/19K.

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“…Interpretation of HAdV detection in pediatric respiratory samples can be difficult, as HAdV (especially species C) is known to establish persistence, with low levels of detection in tonsils and adenoids for years (5,6). Therefore, detection of HAdV in the NP by PCR does not necessarily reflect acute disease in children (10).…”

Section: Filmarray Rp V17 For Detection Of Hadv In Childrenmentioning

confidence: 99%

Performance Characteristics of FilmArray Respiratory Panel v1.7 for Detection of Adenovirus in a Large Cohort of Pediatric Nasopharyngeal Samples: One Test May Not Fit All

et al. 2016

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bThe FilmArray Respiratory Panel (RP) v1.7 assay has improved sensitivity for detection of human adenovirus (HAdV), compared to an earlier version (RP v1.6). RP v1.7 was designed for detection of species B, C, and E but may show variable detection of species A, D, and F. We sought to evaluate the clinical and analytical performance of RP v1.7 for detection of HAdV in a large pediatric cohort. Respiratory specimens obtained from a tertiary care children's hospital between February 2014 and February 2015 were tested for HAdV by RP v1.7. If the RP v1.7 results were negative for HAdV, then the specimens were reflexed to a HAdV-specific laboratory-developed PCR (LD-PCR) assay for confirmation. A subset of specimens underwent secondary confirmatory testing using another commercially available HAdV PCR assay and a molecular typing assay for species identification. Among 4,750 specimens, a total of 146 specimens (3.1%) were HAdV positive by RP v1.7. HAdV was detected by LD-PCR in an additional 220 specimens that were negative by RP v1.7. Overall, a nearly 5% increase in HAdV detection was observed when RP v1.7-negative specimens were reflexed to LD-PCR testing. RP v1.7 did not detect HAdV with either low viral burden (threshold cycle values of >30) or nonrespiratory species (species A, D, and F), as shown in both clinical and analytic data. While the level of sensitivity of RP v1.7 may be adequate for testing among otherwise healthy children, the decreased sensitivity may be problematic for immunocompromised patients, in whom low levels of HAdV in the respiratory tract may precede systemic infection and require early intervention.H uman adenovirus (HAdV) respiratory infections are associated with 7 to 8% of all identified viral causes of acute respiratory illnesses, especially among children under 5 years of age (1, 2). To date, over 50 HAdV serotypes have been identified; they are divided into 7 species (species A to G) and cause a broad spectrum of clinical diseases, due to the organ tropisms of different species. Species A is primarily associated with respiratory and gastrointestinal (GI) infections, species B, C, and E with respiratory infections, species D with ocular and GI infections, and species F and G with GI infections (3, 4). Additionally, HAdV, especially species C, is known to persist for years in human lymphoid tissue (5-7) and may reactivate and replicate under certain conditions (4,8).Clinical interpretation of results for HAdV detection in the nasopharynx (NP) is complicated, in that increased sensitivity is needed in certain populations but increased specificity may be needed in others. For example, even low levels of NP detection in immunocompromised hosts may warrant close monitoring and further intervention (9), as HAdV infections can progress rapidly and cause significant morbidity and mortality in this population (3,4). In contrast, detection of HAdV in otherwise healthy children may not always indicate disease, due to the propensity of HAdV for prolonged shedding and/or persistence in the tonsil...

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Latent Species C Adenoviruses in Human Tonsil Tissues

Abstract: Although species C human adenoviruses establish persistent infections, the molecular details of this lifestyle remain poorly understood. We previously reported that adenovirus DNA is found in human mucosal T lymphocytes in a noninfectious form (

Cited by 183 publications

References 60 publications

Modeling Adenovirus Latency in Human Lymphocyte Cell Lines

Modeling Adenovirus Latency in Human Lymphocyte Cell Lines

Conserved Amino Acids within the Adenovirus 2 E3/19K Protein Differentially Affect Downregulation of MHC Class I and MICA/B Proteins

Performance Characteristics of FilmArray Respiratory Panel v1.7 for Detection of Adenovirus in a Large Cohort of Pediatric Nasopharyngeal Samples: One Test May Not Fit All

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