ICTV Virus Taxonomy Profile: Adenoviridae 2022.

The family Adenoviridae includes non-enveloped viruses with linear dsDNA genomes of 25-48 kb and medium-sized icosahedral capsids. Adenoviruses have been discovered in vertebrates from fish to humans. The family is divided into six genera, each of which is more common in certain animal groups. The outcome of infection may vary from subclinical to lethal disease. This is a summary of the ICTV Report on the family Adenoviridae, which is available at ictv.global/report/adenoviridae.

Interregional Coevolution Analysis Revealing Functional and Structural Interrelatedness between Different Genomic Regions in Human Mastadenovirus D.

UNLABELLED: Human mastadenovirus D (HAdV-D) is exceptionally rich in type among the seven human adenovirus species. This feature is attributed to frequent intertypic recombination events that have reshuffled orthologous genomic regions between different HAdV-D types. However, this trend appears to be paradoxical, as it has been demonstrated that the replacement of some of the interacting proteins for a specific function with other orthologues causes malfunction, indicating that intertypic recombination events may be deleterious. In order to understand why the paradoxical trend has been possible in HAdV-D evolution, we conducted an interregional coevolution analysis between different genomic regions of 45 different HAdV-D types and found that ca. 70% of the genome has coevolved, even though these are fragmented into several pieces via short intertypic recombination hot spot regions. Since it is statistically and biologically unlikely that all of the coevolving fragments have synchronously recombined between different genomes, it is probable that these regions have stayed in their original genomes during evolution as a platform for frequent intertypic recombination events in limited regions. It is also unlikely that the same genomic regions have remained almost untouched during frequent recombination events, independently, in all different types, by chance. In addition, the coevolving regions contain the coding regions of physically interacting proteins for important functions. Therefore, the coevolution of these regions should be attributed at least in part to natural selection due to common biological constraints operating on all types, including protein-protein interactions for essential functions. Our results predict additional unknown protein interactions. IMPORTANCE: Human mastadenovirus D, an exceptionally type-rich human adenovirus species and causative agent of different diseases in a wide variety of tissues, including that of ocular region and digestive tract, as well as an opportunistic infection in immunocompromised patients, is known to have highly diverged through frequent intertypic recombination events; however, it has also been demonstrated that the replacement of a component protein of a multiprotein system with a homologous protein causes malfunction. The present study solved this apparent paradox by looking at which genomic parts have coevolved using a newly developed method. The results revealed that intertypic recombination events have occurred in limited genomic regions and been avoided in the genomic regions encoding proteins that physically interact for a given function. This approach detects purifying selection against recombination events causing the replacement of partial components of multiprotein systems and therefore predicts physical and functional interactions between different proteins and/or genomic elements.

[Bioinformatics on new human adenoviruses causing nosocomial infection].

Human adenovirus (HAdV) causing epidemic keratoconjunctivitis is limited to D and E species. Recent progress in bioinformatics revealed that these viruses attach to the host with fibers, infiltrate the host cells via RGD (Arg-Gly-Asp) motif of penton base, and reveal their serological reaction by hexons. Loops 1 and 2 are the variable regions of each hexon. The possibility that a novel adenovirus later named HAdV-52 was transmitted over the wall of species' from monkeys to humans was reported. The recombination of the above three hot spots introduces novel types such as HAdV-53, -54, and -56. Boinformatics may provide rapid genotyping in nosocomial infection, predicting future epidemics, and an estimate of the therapeutic target molecules in the near future.

Recombination analysis of intermediate human adenovirus type 53 in Japan by complete genome sequence.

Human adenovirus type 53 (HAdV-53) has commonly been detected in samples from epidemic keratoconjunctivitis (EKC) patients in Japan since 1996. HAdV-53 is an intermediate virus, containing hexon-chimeric, penton base and fiber structures similar to HAdV-22 and -37, HAdV-37 and HAdV-8, respectively. HAdV-53-like intermediate strains were first isolated from EKC samples in Japan in the 1980s. Here, the complete genome sequences of three such HAdV-53-like intermediate strains (870006C, 880249C and 890357C) and four HAdV-53 strains were determined, and their relationships were analysed. The seven HAdV strains were classified into three groups, 870006C/880249C, 890357C and the four HAdV-53 strains, on the basis of phylogenetic analyses of the partial and complete genome sequences. HAdV strains within the same group showed the highest nucleotide identities (99.87-100.00 %). Like HAdV-53, the hexon loop 1 and 2 regions of 870006C, 880249C and 890357C showed the highest identity with HAdV-22. However, these strains did not show a hexon-chimeric structure similar to HAdV-22 and -37, or a penton base similar to HAdV-37. The fiber genes of 870006C and 880249C were identical to that of HAdV-37, but not HAdV-8. Thus, the three intermediate HAdVs isolated in the 1980s were similar to each other but not to HAdV-53. The recombination breakpoints were inferred by the Recombination Detection Program (rdp) using whole-genome sequences of these seven HAdV and of 12 HAdV-D strains from GenBank. HAdV-53 may have evolved from intermediate HAdVs circulating in the 1980s, and from HAdV-8, -22 and -37, by recombination of sections cut at the putative breakpoints.

Complete genome analysis of a novel intertypic recombinant human adenovirus causing epidemic keratoconjunctivitis in Japan.

For 4 months from September 2008, 102 conjunctival swab specimens were collected for surveillance purposes from patients across Japan suspected of having epidemic keratoconjunctivitis (EKC). Human adenovirus (HAdV) DNA was detected in 61 samples by PCR, though the HAdV type for 6 of the PCR-positive samples could not be determined by phylogenetic analysis using a partial hexon gene sequence. Moreover, for 2 months from January 2009, HAdV strains with identical sequences were isolated from five conjunctival swab samples obtained from EKC patients in five different regions of Japan. For the analyses of the 11 samples mentioned above, we determined the nucleotide sequences of the entire penton base, hexon, and fiber genes and early 3 (E3) region, which are variable regions among HAdV types, and compared them to those of other HAdV species D strains. The nucleotide sequences of loops 1 and 2 in the hexons of all 11 samples showed high degrees of identity with those of the HAdV type 15 (HAdV-15) and HAdV-29 prototype strains. However, the fiber gene and E3 region sequences showed high degrees of identity with those of HAdV-9, and the penton base gene sequence showed a high degree of identity with the penton base gene sequences of HAdV-9 and -26. Moreover, the complete genome sequence of the 2307-S strain, which was isolated by viral culture from 1 of the 11 samples, was determined. The 2307-S strain was a recombinant HAdV between HAdV-9, -15, -26, -29, and/or another HAdV type; however, the recombination sites in the genome were not obvious. We propose that this virus is a novel intertypic recombinant, HAdV-15/29/H9, and may be an etiological agent of EKC.

Genome variability of human adenovirus type 8 causing epidemic keratoconjunctivitis during 1986-2003 in Japan.

PURPOSE: Epidemic keratoconjunctivitis (EKC) is a contagious acute conjunctivitis associated with community-acquired infection. Human adenovirus type 8 (HAdV-8) is one of the major serotypes isolated from patients with EKC. DNA restriction enzyme analyses were performed to investigate the genetic characteristics of the isolates and their chronological pattern. METHODS: Viral samples were taken from 11 strains isolated from sporadic cases of EKC and identified as HAdV-8 by the neutralization method with type-specific antiserum against HAdV-8 between 1986 and 2003 in Japan. DNA restriction enzyme analysis included six restriction enzymes: BamHI, HindIII, PstI, SacI, SalI, and SmaI. RESULTS: The restriction patterns revealed that the genome types were HAdV-8A and HAdV-8B in 1986, HAdV-8K in 1991, and HAdV-8E in 1996. HAdV-8K was a new genome type revealed with the enzyme SacI. Two strains isolated in 2003 exhibited identical restriction patterns as HAdV-54, which was described in 2008 and collected from Japanese patients in 2000. CONCLUSIONS: Genetic changes might occur chronologically in HAdV-8. HAdV-8 displays considerable variability. The investigations of these variants might be helpful for defining the evolutionary tendency and to predict future outbreaks of HAdV infection.

Disinfectant potential in inactivation of epidemic keratoconjunctivitis-related adenoviruses by potassium peroxymonosulfate.

PURPOSE: The aim of this study was to test the antiviral effectivity of potassium peroxymonosulfate (RUBYSTA®, KYORIN) against five epidemic keratoconjunctivitis-related types of Human adenovirus D in vitro. METHODS: Five types of Human adenovirus D (8, 37, 53, 54 and 56) were incubated with 1% potassium peroxymonosulfate, 0.1% sodium hypochlorite (NaClO) or alcohol-based disinfectant for 30 s or 1 min. These solutions were subjected to measurements of viral titres by infection assays in A549 cells. At day 6 post-infection, both, supernatants and cells, were collected and the viral genome was assessed by real-time polymerase chain reaction analysis. RESULTS: Treatments with 1% potassium peroxymonosulfate led to significant reduction in all tested Human adenovirus D types comparable to disinfecting effects by 0.1% NaClO. Overall, potassium peroxymonosulfate demonstrated sufficient inactivation of the major epidemic keratoconjunctivitis-causing Human adenovirus D to be considered for disinfection and prevention purposes in ophthalmological clinics and hospitals. CONCLUSION: This study demonstrated that potassium peroxymonosulfate is a promising disinfectant for the prevention of epidemic keratoconjunctivitis nosocomial infections in ophthalmological clinics.

Molecular epidemiology of adenoviral keratoconjunctivitis in Saudi Arabia.

PURPOSE: Adenoviral keratoconjunctivitis is a major cause of ocular morbidity and may lead to visual loss. Adenovirus types 8, 19, and 37 may cause epidemic keratoconjunctivitis. The main objective of this study was to determine the types of adenoviruses causing keratoconjunctivitis in Saudi Arabia. METHODS: We conducted a non-interventional observational clinical study. Seventy three eyes from 65 patients who presented to The Eye Center in Riyadh, Saudi Arabia with clinical features of acute adenoviral keratoconjunctivitis were included. Each patient underwent complete clinical examination and features such as membranous reaction, conjunctival hemorrhage, subepithelial corneal infiltrates, and preauricular lymph node enlargement were recorded. Conjunctival swabs were obtained from patients with presumed acute viral conjunctivitis. Immunochromatography (IC) and restriction fragment length polymorphism polymerase chain reaction (PCR-RFLP) were performed on the conjunctival swabs obtained from each eye. Serotype identification was performed using direct sequencing technique. RESULTS: Forty-nine (67.1%) were adenovirus type 8, 8 (11.0%) were adenovirus type 3, 6 (8.2%) type 37, 5 (6.8%) were adenovirus type 4, and 2 (2.3%) type 19. The remaining 5 were types 14, 19, and 22. The prevalence of membranous conjunctivitis was highest (83%) among eyes with adenovirus type 37 while subepithelial corneal opacities were most commonly seen among eyes with adenovirus type 8 (47%). Immunochromatography tests were positive for adenovirus in 48 (65.7%) out of 73 eyes. CONCLUSIONS: This study determined the types of adenoviruses causing keratoconjunctivitis at one center in Saudi Arabia. Direct sequencing techniques is an efficient, accurate, and rapid means of diagnosing adenoviral keratoconjunctivitis. The most common causes of adenoviral keratoconjunctivitis in Saudi Arabia were adenovirus types 8, 3, and 37. Membranous conjunctivitis and subepithelial opacities had the highest frequency of adenovirus types 37 and 8, respectively. Lymph nodes enlargement was least likely in adenovirus type 4.

RETRACTED: Spread of epidemic keratoconjunctivitis due to a novel serotype of human adenovirus in Japan.

This article has been retracted.

[Pathogenesis of infectious conjunctivitis in Nepal].

PURPOSE: We investigated human adenovirus (HAdV) and Chlamydia trachomatis in patients with infectious conjunctivitis in Nepal. METHOD: We obtained swabs from 6 patients with infectious conjunctivitis in a remote area near the Indian border (group A), and from 30 patients at the B. P. Koirala Eye Center of Tribhuvan University Teaching Hospital in Kathmandu (group B). Rapid diagnosis of HAdV was conducted in Nepal, using Capilia adeno eye (Capilia), a rapid adenoviral antigen diagnostic kit using immunochromatography. Residual swabs were brought to Japan and examined for HAdV and Chlamydia trachomatis using polymerase chain reaction (PCR). Etiological analysis of 214 patients with trachoma was also investigated by PCR. RESULTS: Capilia results were negative for the six samples of group A and positive for 13 patients (43%) in group B. PCR showed one (17%) as positive in group A and 30 (100%)in group B. The serotype of all HAdV positive samples was HAdV-8. C serovar of Chlamydia trachomatis was detected in ninety seven cases out of 214 patients with trachoma. CONCLUSION: HAdV-8 and Chlamydia trachomatis serotype C seem to be prevalent in Nepal.

Challenges in management of epidemic keratoconjunctivitis with emerging recombinant human adenoviruses.

Adenoviral epidemic keratoconjunctivitis (EKC) presents as severe conjunctival inflammations involving the cornea that can lead to the development of corneal opacities and blurred vision, which can persist for months. EKC is highly contagious and responsible for outbreaks worldwide, therefore accurate diagnosis and rapid containment are imperative. EKC is caused by a number of types within Human adenovirus species D (HAdV-D): 8, 37 and 64 (formerly known as 19a) and these types were considered the major causes of EKC for over fifty years. Nonetheless, recent improved molecular typing methodologies have identified recombinant HAdV-D types 53, 54 and 56, as newly emerging etiologic agents of EKC infections worldwide. EKC cases due to these recombinant types have potentially been underdiagnosed and underestimated as a source of new EKC outbreaks. Recombination events among circulating HAdV-D types represent a source of new infectious disease threats. Also, the growing number of adenoviral types enabled genomic and phenotypic comparisons to determine pathological properties related to EKC. This review covers the clinical features of EKC, current challenges in clinical practice and recent progress in EKC-related HAdV research, which focuses on the development of novel diagnostic and therapeutic approaches.

Assessment of clinical signs associated with adenoviral epidemic keratoconjunctivitis cases in southern Japan between 2011 and 2014.

Adenoviral epidemic keratoconjunctivitis (EKC) is a major cause of ocular morbidity worldwide and specific antiviral therapies are not available. EKC is primarily caused by Human adenovirus D (HAdV-D) types 8, 37, 53, 54, 56 and 64. Considering the genomic variation in HAdV-D, we hypothesized that clinical signs could be differentiated by virus type. The hypothesis was retrospectively tested with clinical signs recorded from 250 patients with ocular infections visiting an ophthalmological clinic in southern Japan between 2011 and 2014. The results showed that conjunctival opacity, corneal epithelial disorders and pre-auricular lymphadenopathy, were more frequently associated with EKC than other ocular infections. Furthermore, HAdV types 8, 37 and 54, caused corneal complications and longer infections significantly more frequently than infections by types 53 and 56 (P < 0.05). Our descriptive results supported that symptoms severity vary with the infecting type, however, further research is needed to improve diagnosis of EKC.

Novel human adenovirus causing nosocomial epidemic keratoconjunctivitis.

In 2000, we encountered cases of nosocomial infections with epidemic keratoconjunctivitis (EKC) at a university hospital in Kobe, in the western part of Japan. Two human adenovirus (HAdV) strains, Kobe-H and Kobe-S, were isolated from patients with nosocomial EKC infection. They were untypeable by existing neutralizing antisera; however, the isolate was neutralized with homologous antisera. We then encountered several cases of EKC due to nosocomial infections in eye clinics in different parts of Japan. A total of 80 HAdVs were isolated from patients with EKC at eight different hospitals. The partial hexon gene sequences of the isolates were determined and compared to those of the prototype strains of 51 serotypes. All isolates had identical partial hexon nucleotide sequences. Phylogenetic analysis classified these isolates into species of HAdV-D. The isolates showed 93.9 to 96.7% nucleotide identity with HAdV-D prototype strains, while all 32 HAdV-D prototype strains ranged from 93.2 to 99.2% identity. The sequences of the loop 2 and fiber knob regions from the representative strain, Kobe-H, were dissimilar in all prototype strains of 51 serotypes. We believe that this virus is a novel serotype of HAdV that causes EKC.

Epidemic keratoconjunctivitis due to the novel hexon-chimeric-intermediate 22,37/H8 human adenovirus.

In a 2-month period in 2003, we encountered an outbreak of epidemic keratoconjunctivitis (EKC) in Japan. We detected 67 human adenoviruses (HAdVs) by PCR from eye swabs of patients with EKC at five eye clinics in different parts of Japan. Forty-one of the 67 HAdV DNAs from the swabs were identified as HAdV-37 by phylogenetic analysis using a partial hexon gene sequence. When the restriction patterns of these viral genomes were compared with that of the HAdV-37 prototype strain, one isolate showed a never-before-seen restriction pattern. Within 1 year, we encountered three more EKC cases caused by a genetically identical virus: two nosocomial infections at two different university hospitals and a sporadic infection at an eye clinic. We determined the nucleotide sequences of the full-length hexon and fiber genes of these isolates and compared them to those of the 51 prototype strains. Surprisingly, the sequence of the hexon (epsilon determinant) loop-1 and -2 regions showed the highest nucleotide identity with HAdV-22, a rare EKC isolate. However, the nucleotide sequence of the fiber gene was identical to that of the HAdV-8 prototype strain. 22 We propose that this virus is a new hexon-chimeric intermediate HAdV-22,37/H8, and may be an etiological agent of EKC.

Antiadenoviral effect of the alpha 5 beta 1 integrin receptor ligand, GRGDSP peptide, in serotypes that cause acute keratoconjunctivitis.

BACKGROUND/AIMS: In adenoviral conjunctivitis, the infection process starts by the attachment of adenoviral fibers to conjunctival epithelial cells that contain the receptor for the adenovirus. The alpha 5 beta 1 integrin receptor ligand, GRGDSP peptide, contains the arginine-glycine-aspartate-binding motif which is common to the Coxsackie adenovirus receptor and integrins that are known to be adenoviral receptors. We evaluated the antiadenoviral effect of an expected adenoviral receptor inhibitor, GRGDSP peptide,in vitro. METHODS: Adenovirus types 3, 4, 8, 19 and 37 were used. After calculating the 50% cytotoxic concentration of GRGDSP peptide, the adenovirus was cultivated with the agent for 7 days under serial dilution. Adenoviral DNA was qualitatively measured by real-time PCR. RESULTS: GRGDSP peptide showed an inhibitory effect against adenoviral proliferation in all serotypes except type 4 in a dose-dependent manner. CONCLUSION: This result suggests that the alpha 5 beta 1 integrin receptor ligand, GRGDSP peptide, has antiadenoviral activity in vitro, and the possibility of being used for local treatment of epidemic keratoconjunctivitis.

[The study of prevalence of neutralization antibody against human adenovirus in ophthalmological medical workers].

PURPOSE: We studied the prevalence of neutralization antibodies against human adenovirus (hADV) in ophthalmological medical workers as one measure for the prevention of nosocomial infection. METHODS: The prevalence of neutralization antibodies against hADV-3, -4, -7, -8, -11, -19, and -37, which can cause conjunctivitis, was measured in 288 workers at ten ophthamological facilities in Japan. We studied the prevalence in different facilities, different generations, different types of workers (doctors, nurses, and others), and their medical history of hADV conjunctivitis. RESULTS: Among the workers, the prevalence of neutralization antibodies against hADV-3, -4, -7, -8, -11, -19, and -37 was 70.1%, 43.8%, 18.8%, 16.3%, 16.3%, 8.7%, and 6.3%, respectively. The prevalence of neutralization antibodies against hADV-8 was two times higher in doctors than in other workers. People who have a history of hADV conjunctivitis have a high prevalence of neutralization antibodies against hADV-8, -19, and-37. CONCLUSIONS: The prevalence of neutralization antibodies against hADV-8, -19, and-37 was low in the ophthalmological medical workers. These seroepidemiological data indicate the high possibility of an epidemic of conjunctivitis and occurrence of nosocomial infection caused by these serotypes.

Serial Frequencies and Clinical Features of Uveitis in Hokkaido, Japan.

PURPOSE: Environmental and lifestyle changes influence the clinical features of uveitis. This study reviewed the epidemiologic trends of uveitis in the Japanese population. METHODS: A retrospective review of the past 80 years of reports from Hokkaido University Hospital. RESULTS: In the 1930s, tuberculosis accounted for 46% and syphilitic uveitis for 31% of cases. The frequency of these diseases decreased to 12% in the 1950s; 8% in 1969; 0.6% in the 1990s; and 0.8% in the 2000s, while the rate of non-infectious uveitis increased. The three most common specific diagnoses were: sarcoidosis, Vogt-Koyanagi-Harada disease, and Behçet disease. Although Behçet disease was the most frequent non-infectious uveitis until the 1980s, sarcoidosis is now the most frequent cause of newly diagnosed non-infectious uveitis. CONCLUSIONS: The etiology of uveitis has changed with the times. Tubercular and syphilitic cases have greatly decreased, and sarcoidosis is the most frequent type of uveitis today.

Molecular epidemiology of adenoviral conjunctivitis in Hanoi, Vietnam.

PURPOSE: To investigate the serotypes of adenovirus causing conjunctivitis in Hanoi, Vietnam. DESIGN: Clinical diagnosis of adenoviral conjunctivitis and laboratory-based experimental study. METHODS: We collected 21 conjunctival swabs from 21 different patients with a clinical presentation compatible with adenoviral conjunctivitis, in Hanoi, Vietnam. Immunochromatography and real-time polymerase chain reaction (PCR) were performed to detect human adenovirus (HAdV). The sequence of PCR products was analyzed to determine the serotype of HAdV. RESULTS: Of 21 samples, HAdV DNA was detected in 14 samples (66.7%) by real-time PCR. The serotype analysis showed HAdV-8 in 11 samples (78.6%), HAdV-3 in two samples (14.3%), and HAdV-37 in one sample (7.1%). Of 11 HAdV-8 samples, one sample (9.1%) was prototype, and the other 10 samples (90.9%) had identical nucleotide sequence and were identified as a variant of HAdV-8. CONCLUSIONS: HAdV-8 was found to be the predominant serotype in Hanoi, Vietnam. Most of the HAdV-8 samples were a variant of HAdV-8.