Severe Pneumonia Due to Adenovirus Serotype 14: A New Respiratory Threat?

Louie, Janice K.; Kajon, Adriana E.; Holodniy, Mark; Guardia-LaBar, Lilly M.; Lee, Brian; Petru, Ann; Hacker, Jill K.; Schnurr, David P.

doi:10.1086/525261

Cited by 114 publications

(99 citation statements)

References 18 publications

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“…Studies from the United States show that HAdV-B3 and -B7 infections occur more often in adolescents and adults (23,92), while studies from Europe and Asia indicate that these serotypes are also common in children (32,45,90). Since 2005, several outbreaks of HAdV-B14p1 in military facilities and civic communities have been reported in various countries, including the United States, Europe, and Asia (8,48,78). Ads, including HAdV-B3, enter the body via the mouth/nose and generally cause respiratory diseases.…”

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confidence: 99%

A New Human DSG2-Transgenic Mouse Model for Studying the Tropism and Pathology of Human Adenoviruses

Wang

Beyer

Persson

et al. 2012

J Virol

105

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fWe have recently reported that a group of human adenoviruses (HAdVs) uses desmoglein 2 (DSG2) as a receptor for infection. Among these are the widely distributed serotypes HAdV-B3 and HAdV-B7, as well as a newly emerged strain derived from HAdV-B14. These serotypes do not infect rodent cells and could not up until now be studied in small-animal models. We therefore generated transgenic mice containing the human DSG2 locus. These mice expressed human DSG2 (hDSG2) at a level and in a pattern similar to those found for humans and nonhuman primates. As an initial application of hDSG2-transgenic mice, we used a green fluorescent protein (GFP)-expressing HAdV-B3 vector (Ad3-GFP) and studied GFP transgene expression by quantitative reverse transcription-PCR (qRT-PCR) and immunohistochemistry subsequent to intranasal and intravenous virus application. After intranasal application, we found efficient transduction of bronchial and alveolar epithelial cells in hDSG2-transgenic mice. Intravenous Ad3-GFP injection into hDSG2-transgenic mice resulted in hDSG2-dependent transduction of epithelial cells in the intestinal and colon mucosa. Our findings give an explanation for clinical symptoms associated with infection by DSG2-interacting HAdVs and provide a rationale for using Ad3-derived vectors in gene therapy. Human adenoviruses (HAdVs) have been classified into six species (HAdV-A to HAdV-F) currently containing 55 serotypes. Most adenovirus (Ad) serotypes utilize the coxsackie-adenovirus receptor (CAR) as a primary attachment receptor. However, this is not the case for species B Ad serotypes. Species B Ads form two genetic clusters, B1 (HAdV-B3, -B7, -B16, -B21, and -B50) and B2 (HAdV-B11p, -B14, -B34, and -B35) (84). Recently, we have suggested a new grouping of species B Ads based on their receptor usage (82). The members of group 1 (HAdV-B16, -B21, -B35, -B50) nearly exclusively utilize CD46 as a receptor; the members of group 2 (HAdV-B3, -B7, -B14) use a receptor that was unknown until recently (receptor X), group 3 (HAdV-B11p) preferentially interacts with CD46 but also utilizes receptor X if CD46 is blocked or absent. This novel receptor usage-based grouping system has been supported by studies from various groups (27,50,65,66). A newly emerged, pathogenic strain, Ad14-p1, uses the same receptor as prototype HAdV-B14 (89).HAdV-B3 and -B7 are considered to be widely distributed human pathogens (14,52,59). Studies from the United States show that HAdV-B3 and -B7 infections occur more often in adolescents and adults (23, 92), while studies from Europe and Asia indicate that these serotypes are also common in children (32,45,90). Since 2005, several outbreaks of HAdV-B14p1 in military facilities and civic communities have been reported in various countries, including the United States, Europe, and Asia (8,48,78). Ads, including HAdV-B3, enter the body via the mouth/nose and generally cause respiratory diseases. The respiratory tract epithelium is also the preferred site of viral replication. Subsequent virusinduced cyto...

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confidence: 99%

A New Human DSG2-Transgenic Mouse Model for Studying the Tropism and Pathology of Human Adenoviruses

Wang

Beyer

Persson

et al. 2012

J Virol

105

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“…Despite reports of subsequent outbreaks in Europe and Asia during the 1950s and early 1960s ( 6 ), global surveillance in the subsequent decades had not identified circulation of this serotype until spring 2006, when HAdV-14 emerged as a cause of a major proportion of acute febrile respiratory illness in military bases across the United States ( 7 – 9 ). In 2007, community-associated outbreaks were identified in California and New York ( 10 ), and during March–June 2008, ≈140 cases of HAdV-14 were identified in Oregon, Washington, and Texas. Overall, 38% of patients were hospitalized, 17% were admitted to intensive care units, and 5% died.…”

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“…Sequence analysis of the fiber gene of HAdV-14 associated with the recent outbreaks has shown a 6-bp deletion resulting in a 2-aa deletion (lys-glu) at positions 251 and 252 in the knob region compared with the de Wit HAdV-14p prototype strain ( 10 ). The 252glu site is conserved in all other species B HAdVs and is located in the F–G loop of the fiber protein knob near a putative host receptor binding site.…”

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Deaths Associated with Human Adenovirus-14p1 Infections, Europe, 2009–2010

Carr¹,

Kajon²,

Lu³

et al. 2011

Emerg. Infect. Dis.

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Human adenovirus (HAdV) serotype 14 is rarely identified. However, an emerging variant, termed HAdV-14p1, recently has been described in the United States in association with outbreaks of acute respiratory disease with high rates of illness and death. We retrospectively analyzed specimens confirmed positive for HAdV by immunofluorescence, virus culture, or real-time PCR during July 1, 2009–July 31, 2010, and describe 9 cases of HAdV-14p1 infection with characteristic mutations in the fiber and E1A genes that are phylogenetically indistinguishable from the viruses previously detected in the United States. Three patients died; 2 were immunocompromised, and 1 was an immunocompetent adult. We propose that surveillance should be increased for HAdV-14p1 and recommend that this virus be considered in the differential diagnosis of sudden-onset acute respiratory disease, particularly fatal infections, for which an etiology is not clear.

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“…This infection was infrequently reported as an acute respiratory disease in military recruits (Van der Veen & Kok, 1957, Hierholzer & Pumarola, 1976, Metzgar et al, 2007, and recently caused pediatric lower airway disease in Taiwan during (Chen et al, 2002. A new variant of this serotype also caused life-threatening pneumonia in the United States (Louie et al, 2008). Serotype 35 has been detected in urine of patients with acquired immunodeficiency syndrome (AIDS) and other immunodeficiencies (de Jong et al, 1983, Shields et al, 1985, Stalder et al, 1977.…”

Section: Serotypes Of Adenoviruses Inducing Cystitis and Acute Renal mentioning

confidence: 99%