Human Adenovirus Infection Research Articles

Molecular epidemiology of human adenovirus infections in Denmark, 2011–2016

BackgroundHuman adenoviruses (HAdVs) can cause respiratory tract infections, conjunctivitis, diarrhoea and outbreaks have been reported. However, little is known about the disease burden and the molecular epidemiology of HAdV. ObjectivesTo retrospectively perform a molecular characterization of HAdV positive samples received at Statens Serum Institut during the period 2011–2016 and to compare this with demographic information, geographic location, sample collection date and type and co-infection with other viral pathogens. Study design152 HAdV positive samples were genotyped by Sanger sequencing of a fragment of the hexon gene using published primers along with a newly developed primer set for enhanced genotyping of HAdV D. Phylogenetic analysis was used for genotyping and genotypes were compared with epidemiological information. In addition, HAdV burden and co-infection was evaluated for samples tested in laboratory analysis packages. ResultsSix out of seven HAdV species were identified and represented by 13 types. Young children (<5 years old) were more likely to be positive for HAdV and co-infections with other gastrointestinal or respiratory viruses were common. Possible outbreaks of ocular infections due to HAdV D could not be confirmed. ConclusionA diverse set of HAdV species were circulating in Denmark in the study period and although possible transmission clusters were identified, this could not be verified with current genotyping methods Young children were commonly affected by HAdV infection and co-infections with other viral pathogens were frequent suggesting a possible underestimation of the real HAdV burden.

Prospective monitoring of adenovirus infection and type analysis after allogeneic hematopoietic cell transplantation: A single‐center study in Korea

BackgroundEpidemiologic studies of human adenovirus (HAdV) in allogeneic hematopoietic cell transplantation (HCT) recipients have been conducted mostly in European countries where HAdV 2 (species C) has been most prevalent in the community. The main objective of this study was to investigate the epidemiology and the characteristics of HAdV infection in Korean allogeneic HCT recipients (<19 years).MethodsIn a prospective study from April 2012 to September 2015, HAdV in blood, urine, and stool specimens were monitored weekly from transplantation to day 100 or after if clinically suspected. HAdV infection was defined as positive HAdV PCR result in any specimens regardless of symptoms.ResultsA total of 1734 specimens were collected from 57 consecutively enrolled recipients. The cumulative incidence of HAdV infection at day 100, and 1 year was 10%, and 20%, and the incidence of viremia was 2% and 6%, respectively. The median onset time from HCT to viremia was 221 days (range, 7‐596 days). All viremia cases were caused by only HAdV 3 (species B), whereas several types were detected in stool. Among patients with HAdV infection, lower absolute lymphocyte counts and extensive chronic graft‐vs‐host disease were associated with viremia (P = .028 and P = .006, respectively).ConclusionsCompared to western studies, this study demonstrated a lower incidence and delayed onset of HAdV infections and HAdV 3 was most prevalent in Korea.

Sequence typing of human adenoviruses isolated from Polish patients subjected to allogeneic hematopoietic stem cell transplantation – a single center experience

ABSTRACT Purpose: Human adenoviruses (HAdV) from species A, B and C are commonly recognized as pathogens causing severe morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. The purpose of the present study was to determine HAdV types responsible for viremia in HSCT recipients at a large tertiary hospital in Poland. Methods: Analysis of partial nucleotide sequences of HAdV hexon gene was used to type 40 clinical isolates of HAdV obtained from 40 HSCT recipients. Results: We identified six different HAdV serotypes belonging to species B, C and E. We demonstrated high variability in sequences of detected HAdV types, and patients infected with the same HAdV types were not hospitalized at the same time, which suggests the low possibility of cross-infection. In almost all patients, anti-HAdV antibodies in IgG class were detected, which indicates a history of HAdV infection in the past. Clinical symptoms accompanying HAdV viremia were in 89%, and in 61.5% of individuals, HAdV was a sole pathogen detected. There were no cases with high-level HAdV viremia and severe systemic or organ infections. Graft-versus-host disease (GvHD) was present in patients infected with species B and C, but grade II of GvHD was observed only in patients infected with HAdV-B. Conclusions: The predominance of HAdV-C and common presence of anti-HAdV antibodies in IgG class may strongly suggest that most infections in the present study were reactivations of HAdV persisting into the patient’s mucosa-associated lymphoid tissues. Variability of HAdV sequences suggests that cross-infections between patients were very rare. ABBREVIATIONS: GvHD: graft-versus-host disease; HAdV: human adenoviruses; HSCT: hematopoietic stem cell transplantation

Bivalent vaccine platform based on ca influenza virus vaccine elicits protective immunity against human adenoviruses

Human adenoviruses (HAdVs) are prevalent in pediatric and adult patients with severe acute respiratory disease (ARD). To date, there have been no widely used HAdV vaccines available. In this report, we developed a cold-adapted attenuated influenza virus, termed rg HAdV-Flu ca, carrying epitopes from HAdV hexon protein in the backbone of the ca influenza vaccine neuraminidase (NA) gene using reverse genetics. Rg HAdV-Flu ca virus exhibited a cold-adapted (ca) phenotype, and its morphological characteristics were observed using electron microscopy. Moreover, BALB/c mice were immunized intranasally (i.n.) with 105, 106 or 107 TCID50 rg HAdV-Flu ca. Results showed a specific, robust antibody response against influenza and HAdV in a dose-dependent manner. More importantly, potent humoral, mucosal and cellular immune responses protected against subsequent wild-type HAdV-3 or HAdV-7 challenges, as determined by a significant decrease in viral titers and a noticeable alleviation of histopathological alterations in the lung tissue of challenged mice. These findings demonstrate that rg HAdV-Flu ca warrants attention as a potential vaccine candidate against HAdV infection.

Adenovirus types associated with severe respiratory diseases: A retrospective 4-year study in Kuwait.

Human adenovirus (HAdV) infection can result in a severe respiratory disease. The aim of this study was to identify HAdV types detected in patients hospitalized for severe respiratory illness. The study population consisted of 743 patients with severe respiratory disease admitted to four major hospitals in Kuwait between January 2013 and December 2016. Respiratory specimens were retrospectively screened for 20 respiratory viruses by real‐time PCR. The HAdV hexon gene was amplified and directly sequenced, and HAdV types were identified by performing Bayesian phylogenetic analysis. HAdV DNA was detected in 27 (3.6%) patients, with peaks in November and March. Most patients were infants and young children suffering from pneumonia or acute bronchiolitis. The detected HAdV types were C1, C2, C5, B3, and B7. Clusters of HAdV C1, C2, and C5 were observed with high posterior probability. All patients infected with HAdV C5 and 50% of patients infected with HAdV C2 or B7 were admitted to the intensive care unit (ICU). Co‐infection with other viruses was detected in 44.4% of patients. The most common co‐infecting virus was rhinovirus (HRV). HAdV/HRV co‐infection was detected in two children who presumably developed disseminated HAdV infection and died. This is the first report describing the circulation of HAdV types associated with severe outcomes in Kuwait. These findings highlight the need for a national surveillance system to monitor changes in predominant HAdV types and increased numbers of severe respiratory infections.

Species differences in circulation and inflammatory responses in children with common respiratory adenovirus infections.

Human adenoviruses (HAdVs) cause severe inflammatory respiratory infections, but previous epidemiological studies lacked analysis of the characteristics of the inflammation. Consecutive patients <13 years old with acute febrile illness during a 2‐year period were tested. HAdV strains were isolated from nasopharyngeal swabs, and molecular identification was performed by hexon, fiber, and species‐specific PCR methods. Blood inflammatory markers, including the white blood cell (WBC) count, CRP, and 29 cytokines, were measured. A total of 187 patients were enrolled, and HAdV types were identified from 175 patients (93.5%). Species C (types 2, 1, 5, and 6, in order of frequency) was most common at 37.1%, followed by B (type 3) at 30.9% and E (type 4) at 26.9%. Species C was detected predominantly in 1‐year‐old, whereas B and E were in older ages. Species C and B had seasonal circulation patterns, but E was found in only one season during the 2‐year study period. The WBC count was highest in patients with species C. Eleven of the 29 tested serum cytokines were detected. Seven kinds, including G‐CSF, IL‐6, and TNF‐α, were elevated in species C infections, whereas IL‐10 was lowest in species C. Species differences in inflammatory responses, especially regarding serum cytokines were described in common pediatric HAdV infections. Species C causes the strongest inflammatory responses in young children.

Retinoic acid receptor β, a potential therapeutic target in the inhibition of adenovirus replication

Human adenoviruses (HAdVs) usually cause mild respiratory infections, but they can also lead to fatal outcomes for immunosuppressive patients. Unfortunately, there has been no specific anti-HAdV drug approved for medical use. A better understanding of the nature of virus-host interactions during infection is beneficial to the discovery of potential antiviral targets and new antiviral drugs. In this study, a time-course transcriptome analysis of HAdV-infected human lung epithelial cells (A549 cells) was performed to investigate virus–host interactions, and several key host molecules involved in the HAdV infection process were identified. The RARβ (retinoic acid receptor β) molecule, one of the upstream regulatory factors of differentially expressed genes (DEGs), played important roles in HAdV replication. The results of reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting showed that RARβ mRNA and protein were downregulated by HAdV infection in the A549 cells. The knockdown of RARβ by RARβ siRNA increased the HAdV production and the overexpression of RARβ decreased the HAdV production. Furthermore, FDA-approved Tazarotene, which is an RAR selective agonist with relatively more selectivity for RARβ, was found to inhibit HAdV replication in vitro. Taken together, our study presents a key host molecule in adenovirus infection, which could be developed as a potential host target to an anti-adenovirus drug. In addition, this study provides evidence for the re-exploitation of an FDA-approved small molecule for therapeutic applications in adenovirus replication.

577 - Prospective Monitoring of Adenovirus Infection and Type Analysis after Allogeneic Hematopoietic Cell Transplantation: A Single-Center Study in Korea

Background Epidemiologic studies of human adenovirus (HAdV) in allogeneic hematopoietic cell transplantation (HCT) recipients have been conducted mostly in European countries where HAdV 2 (species C) has been most prevalent in the community. The main objective of this study was to investigate the epidemiology and the characteristics of HAdV infection in Korean allogeneic HCT recipients ( Methods In a prospective study from April 2012 to September 2015, HAdV in blood, urine, and stool specimens were monitored weekly from transplantation to day 100 or after if clinically suspected. HAdV infection was defined as positive HAdV PCR result in any specimens regardless of symptoms. Results A total of 1734 specimens were collected from 57 consecutively enrolled recipients. The cumulative incidence of HAdV infection at day 100, and 1 year was 10%, and 20%, and the incidence of viremia was 2% and 6%, respectively. The median onset time from HCT to viremia was 221 days (range, 7-596 days). All viremia cases were caused by only HAdV 3 (species B), whereas several types were detected in stool. Among patients with HAdV infection, lower absolute lymphocyte counts and extensive chronic graft-vs-host disease were associated with viremia (P = .028 and P = .006, respectively). Conclusions Compared to western studies, this study demonstrated a lower incidence and delayed onset of HAdV infections and HAdV 3 was most prevalent in Korea.

Discrimination of Kawasaki disease with concomitant adenoviral detection differentiating from isolated adenoviral infection

PurposeHuman adenovirus infection mimics Kawasaki disease (KD) but can be detected in KD patients. The aim of this study was to determine the clinical differences between KD with adenovirus infection and only adenoviral infection and to identify biomarkers for prediction of adenovirus-positive KD from isolated adenoviral infection.MethodsA total of 147 patients with isolated adenovirus were identified by quantitative polymerase chain reaction. In addition, 11 patients having KD with adenovirus, who were treated with intravenous immunoglobulin therapy during the acute phase of KD were also evaluated.ResultsCompared with the adenoviral infection group, the KD with adenovirus group was significantly associated with frequent lip and tongue changes, skin rash and changes in the extremities. In the laboratory parameters, higher C-reactive protein (CRP) level and presence of hypoalbuminemia and sterile pyuria were significantly associated with the KD group. In the multivariate analysis, lip and tongue changes (odds ratio [OR], 1.416; 95% confidence interval [CI], 1.151–1.741; P=0.001), high CRP level (OR, 1.039; 95% CI 1.743–1.454; P= 0.021) and sterile pyuria (OR 1.052; 95% CI 0.861–1.286; P=0.041) were the significant predictive factors of KD. In addition, the cutoff CRP level related to KD with adenoviral detection was 56 mg/L, with a sensitivity of 81.8% and a specificity of 75.9%.ConclusionLip and tongue changes, higher serum CRP level and sterile pyuria were significantly correlated with adenovirus-positive KD.

Human Adenovirus Surveillance - United States, 2003-2016.

Human adenoviruses (HAdVs) are nonenveloped, double-stranded DNA viruses in the family Adenoviridae; seven species (A-G) and >60 genotypes are known to cause human infection (1). Clinical manifestations associated with HAdV infection include fever, acute respiratory illness, gastroenteritis, and conjunctivitis. HAdV infection can be severe, particularly among immunocompromised patients, and can cause respiratory failure, disseminated infection, hemorrhagic cystitis, neurologic disease, and death (1,2). Illness tends to occur sporadically and without demonstrated seasonality. Outbreaks of HAdV have been reported globally in communities (3), and in closed or crowded settings, including dormitories, health care settings, and among military recruits, for whom a vaccine against HAdV type 4 (HAdV-4) and HAdV type 7 (HAdV-7) has been developed (4,5). CDC summarized HAdV detections voluntarily reported through the National Adenovirus Type Reporting System (NATRS) after initiation of surveillance in 2014 to describe trends in reported HAdVs circulating in the United States. Reporting laboratories were also encouraged to report available results for specimens collected before surveillance began. Overall, the number of reporting laboratories and HAdV type identifications reported to NATRS has increased substantially from the start of official reporting in 2014 through 2016; this report describes specimens collected during 2003-2016. The most commonly reported HAdV types were HAdV type 3 (HAdV-3) and HAdV type 2 (HAdV-2), although HAdV types reported fluctuated considerably from year to year. In the United States, information on recently circulating HAdV types is needed to inform diagnostic and surveillance activities by clinicians and public health practitioners. Routine reporting to NATRS by all U.S. laboratories with the capacity to type HAdVs could help strengthen this surveillance system.

Human Adenovirus (HAdV) Viremia in Immunocompetent Children with HAdV Infection in Respiratory Specimens: Does Viremia Predict Severity of Illness?

BackgroundThe interpretation of HAdV PCR from upper respiratory tract (RT) specimens can be challenging due to prolonged low grade viral shedding. We hypothesized that HAdV detection in the blood (viremia) is more common in acute HAdV infection with high respiratory viral burden (VB) compared with those with low VB in the RT. We sought to determine the frequency of HAdV viremia in immunocompetent children who have detectable HAdV in the RT.MethodsWe prospectively identified + HAdV in RT specimens from emergency department or inpatients using semi-quantitative real-time PCR (Ct <40) or multiplex respiratory viral PCR (FILMARRAY RESPIRATORY PANEL v1.7) and prospectively collected available whole blood from 8/2013 to 2/2015. Blood was considered positive for HAdV if Ct was <40 in whole blood. We compared virologic, including HAdV type from the RT and blood, and clinical characteristics between viremic and non-viremic groups using Mann–Whitney or chi-square as appropriate.ResultsThere were 196 unique patients with + HAdV in RT specimens as well as available blood for PCR (median age=1.3 years old). Blood and RT samples were obtained on the same calendar day in 78% of patients. Among these 196 patients, 163 (83%) were hospitalized and 58 (36%) were admitted to PICU. HAdV was detected in the blood in 33% of patients. Upper respiratory tract infections were more common (P = 0.026) and the duration of fever at the time of enrollment was longer in the viremia group (3 vs. 2 days, P = 0.043). There was no difference in ICU admission between two groups. Coinfections with bacterial pathogens from sterile sites were only found in the non-viremic group (4%); these included S. aureus or pneumococcal bacteremia, E. coli urinary tract infections, or pneumococcal pneumonia. HAdV VB in RT were significantly higher in the viremia group (Ct median 25.01 vs.. 36.38, P < 0.0001). Species C was more predominant in the viremia group compared with non C (A, B/E, D, F) (P = 0.018). RT type was 100% concordant with blood type.ConclusionHAdV viremia is relatively common in immunocompetent children with HAdV infection in the RT. Subjects with viremia had significantly higher VB in the RT, but this didn’t seem to be correlated with disease severity. HAdV viremia may be useful tool to add further evidence of acute HAdV infection.Disclosures A. Leber, BioFIre Diagnostics: Research Contractor and Scientific Advisor, Research support, Speaker honorarium and Travel expenses

Anti-adenoviral Artificial MicroRNAs Expressed from AAV9 Vectors Inhibit Human Adenovirus Infection in Immunosuppressed Syrian Hamsters.

Infections of immunocompromised patients with human adenoviruses (hAd) can develop into life-threatening conditions, whereas drugs with anti-adenoviral efficiency are not clinically approved and have limited efficacy. Small double-stranded RNAs that induce RNAi represent a new class of promising anti-adenoviral therapeutics. However, as yet, their efficiency to treat hAd5 infections has only been investigated in vitro. In this study, we analyzed artificial microRNAs (amiRs) delivered by self-complementary adeno-associated virus (scAAV) vectors for treatment of hAd5 infections in immunosuppressed Syrian hamsters. In vitro evaluation of amiRs targeting the E1A, pTP, IVa2, and hexon genes of hAd5 revealed that two scAAV vectors containing three copies of amiR-pTP and three copies of amiR-E1A, or six copies of amiR-pTP, efficiently inhibited hAd5 replication and improved the viability of hAd5-infected cells. Prophylactic application of amiR-pTP/amiR-E1A- and amiR-pTP-expressing scAAV9 vectors, respectively, to immunosuppressed Syrian hamsters resulted in the reduction of hAd5 levels in the liver of up to two orders of magnitude and in reduction of liver damage. Concomitant application of the vectors also resulted in a decrease of hepatic hAd5 infection. No side effects were observed. These data demonstrate anti-adenoviral RNAi as a promising new approach to combat hAd5 infection.

Epidemic and molecular characteristic of human adenovirus infection among patients with febrile respiratory syndrome from a hospital in Qinghai Province, 2012-2015

Epidemic and molecular characteristic of human adenovirus infection among patients with febrile respiratory syndrome from a hospital in Qinghai Province, 2012-2015

Expression profile of Epstein-Barr virus and human adenovirus small RNAs in tonsillar B and T lymphocytes.

We have used high-throughput small RNA sequencing to characterize viral small RNA expression in purified tonsillar B and T lymphocytes isolated from patients tested positive for Epstein-Barr virus (EBV) or human adenovirus (HAdV) infections, respectively. In the small set of patients analyzed, the expression profile of EBV and HAdV miRNAs could not distinguish between patients diagnosed with tonsillar hypertrophy or chronic/recurrent tonsillitis. The EBV miR-BART expression profile among the patients diagnosed with tonsillar diseases resembles most closely the pattern seen in EBV+ tumors (Latency II/I). The miR-BARTs that appear to be absent in normal EBV infected cells are essentially all detectable in the diseased tonsillar B lymphocytes. In the EBV+ B cells we detected 44 EBV miR-BARTs derived from the proposed BART precursor hairpins whereof five are not annotated in miRBase v21. One previously undetected miRNA, BART16b-5p, originates from the miR-BART16 precursor hairpin as an alternative 5´ miR-BART16 located precisely upstream of the annotated miR-BART16-5p. Further, our analysis revealed an extensive sequence variation among the EBV miRNAs with isomiRs having a constant 5´ end but alternative 3´ ends. A range of small RNAs was also detected from the terminal stem of the EBER RNAs and the 3´ part of v-snoRNA1. During a lytic HAdV infection in established cell lines the terminal stem of the viral non-coding VA RNAs are processed to highly abundant viral miRNAs (mivaRNAs). In contrast, mivaRNA expression in HAdV positive tonsillar T lymphocytes was very low. The small RNA profile further showed that the 5´ mivaRNA from VA RNAI and the 3´ mivaRNA from VA RNAII were as predicted, whereas the 3´ mivaRNA from VA RNAI showed an aberrant processing upstream of the expected Dicer cleavage site.

Simultaneous development of Kawasaki disease following acute human adenovirus infection in monozygotic twins: A case report

BackgroundThe etiology of Kawasaki disease (KD) remains unknown. However, many studies have suggested that specific genetic factors and/or some infectious agents underlie the onset of KD. Previous studies have suggested that human adenovirus (HAdV) is one of the triggering pathogens of KD. Here, we report monozygotic twin boys who sequentially developed KD in conjunction with acute HAdV type 3 (HAdV-3) infection.Case presentationThe patients were four-year-old monozygotic twin boys. The elder brother developed a high fever and was diagnosed with HAdV infection with an immunochromatographic kit for HAdV (IC-kit). He was transferred to our institute after persistent fever for 7 days. On admission, he already fulfilled all the diagnostic criteria for KD. His laboratory data were as follows: WBC, 9700/μl; CRP, 2.42 mg/dl; IFN-γ, 99.8 pg/ml; and TNF-α, 10.9 pg/ml. He received intravenous immunoglobulin (IVIG) and aspirin and responded well, with no coronary artery abnormalities. The younger brother, who was also IC-kit-positive, was hospitalized on the same day as his elder brother after persistent fever for 3 days. His data on admission were as follows: WBC, 12,600/μl; CRP, 5.54 mg/dl; IFN-γ, 105.0 pg/ml; and TNF-α, 33.6 pg/ml. Although he developed all of the typical KD symptoms by day 4, his fever subsided spontaneously on day 6 without IVIG or aspirin. However, he developed a dilation of the coronary artery in the region of the left circumflex artery bifurcation on day 10. His coronary artery dilation had resolved 3 months after onset. HAdV-3 DNA was detected with PCR in stool samples from both patients, and HAdV3 was isolated from the younger brother’s stool sample. Serum neutralizing antibodies to AdV3 were also significantly elevated in both patients, suggesting seroconversion.ConclusionsThere have been few reports of the simultaneous development of KD in monozygotic twins. Notably, both twins had an acute HAdV-3 infection immediately before they developed KD. These cases strongly suggest that KD was triggered by HAdV-3 infection, and they indicate that specific immune responses to some pathogens (such as HAdV-3), arising from genetic susceptibility, play a critical role in the pathogenesis of KD.

A Report of Adult Human Adenovirus Infections in a Tertiary Hospital.

We describe a review of human adenovirus (HAdV) infections occurring among adults in a tertiary hospital in Singapore from February to May 2013. A similar increase in cases was observed among children and military personnel during the same time period. The majority of isolates were identified as HAdV-7, likely an emerging pathogen in Asia.

Mechanisms of pathogenesis of emerging adenoviruses.

Periodic outbreaks of human adenovirus infections can cause severe illness in people with no known predisposing conditions. The reasons for this increased viral pathogenicity are uncertain. Adenoviruses are constantly undergoing mutation during circulation in the human population, but related phenotypic changes of the viruses are rarely detected because of the infrequency of such outbreaks and the limited biological studies of the emergent strains. Mutations and genetic recombinations have been identified in these new strains. However, the linkage between these genetic changes and increased pathogenicity is poorly understood. It has been observed recently that differences in virus-induced immunopathogenesis can be associated with altered expression of non-mutant viral genes associated with changes in viral modulation of the host innate immune response. Initial small animal studies indicate that these changes in viral gene expression can be associated with enhanced immunopathogenesis in vivo. Available evidence suggests the hypothesis that there is a critical threshold of expression of certain viral genes that determines both the sustainability of viral transmission in the human population and the enhancement of immunopathogenesis. Studies of this possibility will require extension of the analysis of outbreak viral strains from a sequencing-based focus to biological studies of relationships between viral gene expression and pathogenic responses. Advances in this area will require increased coordination among public health organizations, diagnostic microbiology laboratories, and research laboratories to identify, catalog, and systematically study differences between prototype and emergent viral strains that explain the increased pathogenicity that can occur during clinical outbreaks.

α-Defensin HD5 Inhibits Human Papillomavirus 16 Infection via Capsid Stabilization and Redirection to the Lysosome.

ABSTRACTα-Defensins are an important class of abundant innate immune effectors that are potently antiviral against a number of nonenveloped viral pathogens; however, a common mechanism to explain their ability to block infection by these unrelated viruses is lacking. We previously found that human defensin 5 (HD5) blocks a critical host-mediated proteolytic processing step required for human papillomavirus (HPV) infection. Here, we show that bypassing the requirement for this cleavage failed to abrogate HD5 inhibition. Instead, HD5 altered HPV trafficking in the cell. In the presence of an inhibitory concentration of HD5, HPV was internalized and reached the early endosome. The internalized capsid became permeable to antibodies and proteases; however, HD5 prevented dissociation of the viral capsid from the genome, reduced viral trafficking to the trans-Golgi network, redirected the incoming viral particle to the lysosome, and accelerated the degradation of internalized capsid proteins. This mechanism is equivalent to the mechanism by which HD5 inhibits human adenovirus. Thus, our data support capsid stabilization and redirection to the lysosome during infection as a general antiviral mechanism of α-defensins against nonenveloped viruses.

Investigation of viral infection in idiopathic pulmonary fibrosis among Iranian patients in Tehran.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease, which can be lethal with chronic complications. Viral infections may be associated with IPF and other fibrotic lung diseases. In the present study, we investigate for the first time in Iran the related viral etiology of IPF in order to detect three respiratory viruses; human adenovirus, enterovirus and bocavirus. In this cross-sectional study which was supported by Iran University of Medical Sciences, Tehran, Iran. The diagnostic criteria for IPF were based on internationally accepted clinical and imaging criteria in accordance with the 2011 IPF guidelines. 30 nasopharyngeal (NP) swabs or broncho-alveolar lavage (BAL) samples were obtained from the lung of IPF patients that were diagnosed by a sophisticated practitioner from April 2015 to February 2016. Real-time (RT) polymerase chain reaction (PCR) method was performed to detect the three viruses. Fluorescence dye of a labeled probe recorded the results in order to create positive and negative controls. SPSS version 20 software was used to calculate basic descriptive and frequency features. Of 30 specimens, 13 (43.4%) were male and 17 (56.6%) were female with the total mean age±standard deviation 68.2±12.0. RT-PCR assay results illustrated there was no infection of human adenovirus, enterovirus, and bocavirus detected in these samples. Significant results between IPF incidence and variables were not significant (p>0.05). The causes of IPF in Iranian patients need more research although, based on the results of this study, there was no association between human adenovirus, enterovirus, bocavirus, and IPF.

Surveillance of Adenovirus Respiratory Infections in Children from Osaka, Japan.

Human adenovirus (HAdV) strains isolated from respiratory specimens of 139 children were analyzed to evaluate the endemic situation of HAdV infections in Osaka, Japan, between 2008 and 2015. The cases increased during spring and winter, and the infections were confirmed mainly in children aged ≤ 5 years, comprising 91.9% of the total population examined. Molecular typing of the isolates revealed that the most common types belonged to HAdV-B and -C. Co-infection of HAdV-C1 and -C2 was also confirmed in a case. The median age of HAdV-E cases was higher than that of the HAdV-B and -C cases. These results revealed age and seasonal distribution of respiratory HAdV infections in children from Osaka, and indicate that majority of these children might have acquired immunity through endemic HAdV infection before reaching school age.