Acute and Chronic Human Adenovirus Pneumonia: Cellular and Extracellular Matrix Components

Rosman, Fernando Colonna; Mistchenko, Alicia; Ladenheim, Hilda S.; Nascimento, Jussara Pereira do; Outani, Heloísa Novaes; Madi, Kalil; Lenzi, Henrique Leonel

doi:10.1080/15513819609168688

Cited by 9 publications

(4 citation statements)

References 62 publications

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“…Serotypes most commonly found are 1, 2, 5 and 6 from group C and 3 from group B [6,11]. Adenovirus accounts for 10% of pneumonias in this population [2] and the serotypes isolated from the lungs include 1, 2, 3, 5, 7 [12] and 21 [13,14]. In situ hybridization showed that alveolar and bronchiolar epithelial cells are infected by adenovirus in pneumonias [15] (Figure 2).…”

Section: Pediatric Populationmentioning

confidence: 99%

Adenovirus infections and lung disease

Hayashi¹,

Hogg²

2007

Current Opinion in Pharmacology

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Adenovirus, particularly its E1A protein, has been investigated in the pathogenesis of chronic obstructive pulmonary disease (COPD). High levels of E1A DNA were found in the lungs of COPD patients, where its expression increased with disease severity. In lung epithelial cells, E1A increased intercellular adhesion molecule-1 and interleukin-8 expression, as well as nuclear factor-kappaB activation, in response to inflammatory stimuli. In addition to regulating the mediators that promote emphysema, E1A upregulates transforming growth factor-beta1 expression in bronchiolar epithelial cells and transforms lung epithelial cells to express mesenchymal markers. These results support its additional role in the airway remodeling process reported in COPD.

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Section: Pediatric Populationmentioning

confidence: 99%

Adenovirus infections and lung disease

Hayashi¹,

Hogg²

2007

Current Opinion in Pharmacology

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“…in immunocompetent individuals, the infection may lead to fatal pneumonia in young children (4)(5)(6)(7). It was reported that more than 20% of hospitalized children with acute respiratory tract infections had HAdV (1,8,9), with species C as the unique pathogen in children with acute bronchiolitis or recurrent wheezing (8).…”

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confidence: 99%

Histone Deacetylase Inhibitors Promote Latent Adenovirus Reactivation from Tonsillectomy Specimens

Wang

Zhang

et al. 2020

J Virol

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Adenovirus (HAdV) infection is a common cause of illness among young children, immunocompromised patients, and transplant recipients. The majority of HAdV infections are self-limited, but recurring infection is frequently encountered in young children and may require hospitalization. In this study, we surveyed the presence of HAdV in tonsillectomy samples and investigated epigenetic conditions that contributed to HAdV reactivation. HAdV DNA was detected from 86.7% donors. The lymphocytes isolated from the samples failed to produce infectious HAdV after incubation, suggesting the viruses remained in a latent status. To determine whether epigenetic factors played a role in HAdV reactivation, isolated lymphocytes were treated with a small compound library. Viral DNA replication and infectious HAdV production were assayed by PCR and by a secondary infection assay. We identified several compounds, mainly pan- and selective histone deacetylase (HDAC) inhibitors, which showed activity to reactivate HAdV from latency. The viruses were isolated and were determined as species C HAdV. Using a model of HAdV lytic infection, we showed that the compounds promoted histone-3 acetylation and association with viral early gene promoters. In addition to demonstrate the palatine tonsils as a reservoir of latent HAdV, this study uncovers a critical role of histone acetylation in HAdV reactivation, linking HAdV latency to recurrent HAdV infection. IMPORTANCE Respiratory tract infection by adenoviruses is among the most common diseases in children, attributing to approximately 20% of hospitalizations of children with acute respiratory infection (ARI). Adenovirus transmits by direct contact, but recurrent infection is common. Ever since its isolation, adenovirus has been known to have the ability to establish persistent or latent infection. We found 87.7% tonsillectomy specimens contained detectable amounts of adenoviral DNA. Isolated lymphocytes did not produce infectious adenoviruses without stimulation. By screening an epigenetic informer compound library, we identified several histone deacetylase inhibitors that promoted adenovirus reactivation that was evidenced by increased viral DNA replication and production of infectious viruses. The human tonsils are covered with bacterial pathogens that may utilize pathogen-associated pattern molecules or metabolites to cause epigenetic activation and proinflammatory gene transcription, which may lead to viral reactivation from latency. The study shows that recurrent adenovirus infection could arise from reactivation of residing virus from previous infections.

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“…However, important exceptions exist. Adenovirus infections of very young children can lead to fatal pneumonia (8,33,50). Up to half of cases of intussusception (a bowel obstruction commonly caused by lymphoid hyperplasia) in children under the age of 2 are associated with the common adenoviruses (22,43,48).…”

mentioning

confidence: 99%