A Novel Mastadenovirus from Nyctalus noctula Which Represents a Distinct Evolutionary Branch of Viruses from Bats in Europe.

Bats are natural hosts of a wide variety of viruses, including adenoviruses. European bats are known to carry mastadenoviruses categorized as species B (widespread in European Vespertilionidae bats) and whose taxonomy has not been clarified. We examined fecal samples from Vespertilionidae bats (five species) captured in central Russia and found that 2/12 (16%) were positive for mastadenoviruses. The partial genome of the mastadenovirus was assembled from Pipistrellus nathusii, representing the bat adenovirus species B. The complete genome (37,915 nt) of a novel mastadenovirus was assembled from Nyctalus noctula and named BatAdV/MOW15-Nn19/Quixote. Comparative studies showed significant divergence of the Quixote genome sequence from European bat mastadenoviruses, while the only known virus showing low similarity was the isolate WA3301 from an Australian bat, and together they formed a subclade that separated from other BatAdVs. Phylogenetic and comparative analysis of the protein-coding genes provided evidence that Quixote is related to a novel species within the genus Mastadenovirus, provisionally named "K" (as the next available letter for the species). Phylogenetic analyses revealed that some earlier viruses from Western European bats, for which only partial DNA polymerase genes are known, are most likely members of the tentatively named species "K". Thus, at least two species of mastadenovirus are circulating in bats throughout Europe, from western to eastern areas.

Whole genome analysis of Human Mastadenovirus D causing Keratoconjunctivitis in India - A multicentre study.

INTRODUCTION: Human mastadenovirus (HAdV) types 8, 37, 64 have been considered the major contributors in Epidemic keratoconjunctivitis (EKC) epidemics, but recent surveillance data have shown the involvement of emerging recombinants, including HAdV-53, HAdV-54, and HAdV-56. In our initial work, positive samples for adenovirus revealed that our strains were closer to HAdV-54 than HAdV-8. Hence, the current study aimed to use whole genome technology to identify the HAdV strain correctly. METHODOLOGY: Oxford Nanopore technique was used, wherein a Targeted sequencing approach using long-range PCR amplification was performed. Primers were designed using HAdV-54 (AB448770.2) and HAdV-8 (AB897885.1) as reference sequences. Amplicons were sequenced on the GridION sequencer. Sequences were annotated using Gatu software, and similarities with standard reference sequence was calculated using Bioedit software. The phylogenetic tree was built after alignment in MEGA v7.0 using Neighbour joining method for each of the genes: Penton, Hexon, and Fiber. The effect of novel amino acid changes was evaluated using the PROVEAN tool. The Recombination Detection Program (RDP) package Beta 4.1 was used to identify recombinant sequences. RESULTS: Of the five samples sequenced, OL450401, OL540403, and OL540406 showed nucleotide similarity to HAdV-54 in the penton region. Additionally, OL450401 showed a statistically significant recombination event with HAdV-54 as minor and HAdV-8 as major parents. This was further supported by phylogenetic analysis as well. CONCLUSIONS: In the present study, we have found evidence of a shift from HAdV-8 towards HAdV-54, thus stressing the need for surveillance of HAdVs and to stay updated on the rise of new recombinants.

Identification of a novel adenovirus in liver tissue sample of the Great Himalayan leaf-nosed bat (Hipposideros armiger).

Bats are important reservoirs for many zoonotic viruses. To explore and monitor potential novel viruses carried by bats, 21 liver samples of bats (Hipposideros armiger) were collected from Yunnan Province in southern China. Only one (4.8%) of all models was detected with adenovirus. The whole genome strain obtained by the viral metagenomics method combined with PCR was temporarily named YN01. The complete genome of YN01 was 37,676 bp, with a G + C content of 55.20% and 28 open reading frames. Phylogenetic analysis indicated that the strain YN01 can be classified as genus Mastadenovirus and was the most similar to the adenovirus isolated from Rhinolophus sinicus in China in 2016. The analysis is needed to verify the possibility of cross-species transmission. This virological investigation has increased our understanding of the ecology of bat-borne viruses in this area and provided a reference for possible future infectious diseases.

Genetic diversity of adenovirus in neotropical bats from Brazil.

Bats can harbor a diversity of viruses, such as adenovirus. Ten different species of bat adenoviruses (BtAdV A to J) have been previous described worlwide. In Brazil, BtAdV was described in three species of phyllostomid species: Artibeus lituratus, Desmodus rotundus, and Sturnira lilium. There are around 180 bat species in Brazil, with 67% inhabiting the Atlantic Forest, with few information about the circulation of BtAdV in this biome. We aimed to describe the molecular detection and the phylogenetic characterization and suggest a classification of BtAdVs circulating in bats from the Brazilian Atlantic Forest. We collected 382 oral and rectal swabs from 208 bats between 2014-2015 and 2020-2021 from São Paulo, Pernambuco, and Santa Catarina Brazilian states. The adenovirus detection was done by a nested PCR targeting the DNA polymerase gene, and all positive samples were sequenced by the Sanger method. The phylogenetic analyses were based on the amino acid sequences using the MEGA 7 and BEAST software. We obtained 16 positive animals (detection rate 7.7%) belonging to seven bat species: Artibeus lituratus, Carollia perspicillata, Sturnira lilium, Molossus molossus, and the first record of Phyllostomus discolor, Eptesicus diminutus, and Myotis riparius. The phylogenetic analysis based on partial amino acid sequences showed that all obtained AdV sequences belong to the Mastadenovirus genus. We observed a high genetic diversity of BtAdV and identified eleven potential BtAdV species circulating in Brazil (BtAdV K to U). Our results contribute to the epidemiological surveillance of adenovirus, increasing the knowledge about the viral diversity and the distribution of AdV in bats from the Atlantic Forest.

Outbreak of adenovirus D8 in a neonatal intensive care unit involving multiple simultaneous transmission pathways.

BACKGROUND: Adenovirus (ADV) outbreaks in neonatal intensive care units (NICU) can lead to durable transmission and serious adverse outcomes. This study describes the investigation and control of an ADV-D8 outbreak in an NICU, associated with ophthalmologic equipment used during retinopathy of prematurity (ROP) screening. Cases were observed in neonates, parents and nurses. METHODS: The outbreak investigation was performed including sampling patients, parents and health care workers as well as the environment for molecular detection of ADV DNA. The investigation was also conducted in the guest house where some parents were temporary residents. A retrospective cohort study focused on neonates hospitalized during the epidemic period to assess the risk associated with ROP examination. RESULTS: Fifteen cases were identified in neonates; all but one presented with conjunctivitis. Two healthcare workers and 18 parents acquired conjunctivitis. ADV DNA was identified on the RetCam and on the freezer shared by parents. All ADV-positive samples were typed as ADV-D8. ADV infections occurred more frequently in neonates who had ROP examinations (37.8% (14/37) vs (0.9% (1/110); P<0.001) (relative risk 41.6; (5.7-305.8)). The RetCam was disinfected between two examinations using a disinfectant that was virucidal on ADV after a 30-min contact. CONCLUSION: This outbreak was significantly associated with ROP examination with a RetCam that had a disinfection protocol ill-adapted to rapid patient turnover. In addition, nosocomial transmission via the parents to neonates and parent-to-parent transmission is likely to have played a role in the dissemination of cases. No further cases were observed after the new disinfection procedure was enforced.

Detection and Molecular Characterization of Adenoviruses in Captive and Free-Roaming African Green Monkeys (Chlorocebus sabaeus): Evidence for Possible Recombination and Cross-Species Transmission.

In the present study, 31 samples (12 fecal, 9 nasal and 10 rectal swabs) from 28/92 (30.43%, 10 captive and 18 free-roaming African green monkeys (AGMs, Chlorocebus sabaeus)) apparently healthy AGMs in the Caribbean Island of St. Kitts tested positive for adenoviruses (AdVs) by DNA-dependent DNA polymerase (pol)-, or hexon-based screening PCR assays. Based on analysis of partial deduced amino acid sequences of Pol- and hexon- of nine AGM AdVs, at least two AdV genetic variants (group-I: seven AdVs with a Simian mastadenovirus-F (SAdV-F)/SAdV-18-like Pol and hexon, and group-II: two AdVs with a SAdV-F/SAdV-18-like Pol and a Human mastadenovirus-F (HAdV-F)/HAdV-40-like hexon) were identified, which was corroborated by analysis of the nearly complete putative Pol, complete hexon, and partial penton base sequences of a representative group-I (strain KNA-08975), and -II (KNA-S6) AdV. SAdV-F-like AdVs were reported for the first time in free-roaming non-human primates (NHPs) and after ~six decades from captive NHPs. Molecular characterization of KNA-S6 (and the other group-II AdV) indicated possible recombination and cross-species transmission events involving SAdV-F-like and HAdV-F-like viruses, corroborating the hypothesis that the evolutionary pathways of HAdVs and SAdVs are intermingled, complicated by recombination and inter-species transmission events, especially between related AdV species, such as HAdV-F and SAdV-F. To our knowledge, this is the first report on detection and molecular characterization of AdVs in AGMs.

Deer mastadenovirus B pneumonia in a white-tailed deer fawn.

A 7-mo-old farmed white-tailed deer fawn (Odocoileus virginianus) died after several weeks of progressive deterioration associated with endoparasitism and respiratory signs. A field autopsy was performed, and lung tissue was submitted for histologic examination. The findings were consistent with necrosuppurative bronchointerstitial pneumonia with intranuclear viral inclusions. Immunofluorescence using fluorescently labeled polyclonal antibodies to bovine adenovirus 3 and 5 was positive. To rule out cross-reactivity with other adenoviruses, formalin-fixed, paraffin-embedded tissue sections were submitted for genome sequence analysis, which revealed a 99.6% match to Deer mastadenovirus B (formerly Odocoileus adenovirus 2, OdAdV2). To our knowledge, natural clinical disease associated with OdAdV2 has not been reported previously.

Seroprevalence of neutralizing antibodies to human mastadenovirus serotypes 3 and 7 in healthy children from guangdong province.

Severe adenovirus pneumonia is becoming more common in children infected with human mastadenovirus (HAdV)-3 and HAdV-7 than in those infected with other types of adenoviruses. Recently, there has been a trend toward an increasing prevalence of pneumonia caused by HAdV-7, an important viral pathogen in Pediatric Intensive Care Unit infections. Children infected with HAdV-7 have more serious symptoms of acute respiratory infections and other complications than those infected with HAdV-3. No specific anti-adenovirus drugs or vaccines are available for treatment or prevention. Therefore, we investigated the seroprevalence and titer levels of neutralizing antibodies (NAbs) against HAdV-3 and HAdV-7 in healthy children in Guangdong Province. We found that the seropositivity rates and antibody titers for HAdV-3 NAb were higher than those for HAdV-7 NAb. In children between 6 and 12 months of age, the seropositivity rates and titers were significantly low against HAdV-3 and HAdV-7. The HAdV-7-positive rate was significantly higher in the HAdV-3-positive samples than in the HAdV-3-negative samples. The HAdV-7 NAbs carried by the 0-6-month age group were dominated by low titers. These results reveal a low level of herd immunity against HAdV-3 and HAdV-7 in children, clarifying the importance of monitoring these two highly virulent adenoviruses, developing prophylactic vaccines, and predicting potential outbreaks.

Detection and genetic characterization of enteric viruses in diarrhoea outbreaks from swine farms in Spain.

BACKGROUND: The aim of this work was to study the prevalence and distribution of Porcine astrovirus (PAstV), Porcine kobuvirus (PKoV), Porcine torovirus (PToV), Mammalian orthoreovirus (MRV) and Porcine mastadenovirus (PAdV) as well as their association with widely recognized virus that cause diarrhoea in swine such as coronavirus (CoVs) and rotavirus (RVs) in diarrhoea outbreaks from Spanish swine farms. Furthermore, a selection of the viral strains was genetically characterized. RESULTS: PAstV, PKoV, PToV, MRV and PAdV were frequently detected. Particularly, PAstV and PKoV were detected in almost 50% and 30% of the investigated farms, respectively, with an age-dependent distribution; PAstV was mainly detected in postweaning and fattening pigs, while PKoV was more frequent in sucking piglets. Viral co-infections were detected in almost half of the outbreaks, combining CoVs, RVs and the viruses studied, with a maximum of 5 different viral species reported in three investigated farms. Using a next generation sequencing approach, we obtained a total of 24 ARN viral genomes (> 90% genome sequence), characterizing for first time the full genome of circulating strains of PAstV2, PAstV4, PAstV5 and PToV on Spanish farms. Phylogenetic analyses showed that PAstV, PKoV and PToV from Spanish swine farms clustered together with isolates of the same viral species from neighboring pig producing countries. CONCLUSIONS: Although further studies to evaluate the role of these enteric viruses in diarrhoea outbreaks are required, their wide distribution and frequent association in co-infections cannot be disregard. Hence, their inclusion into routine diagnostic panels for diarrhoea in swine should be considered.

Detection and Phylogenetic Characterization of a Novel Adenovirus Found in Lesser Mouse-Eared Bat (Myotis blythii) in South Kazakhstan.

Bats are an important natural reservoir of various pathogenic microorganisms, and regular monitoring is necessary to track the situation of zoonotic infections. When examining samples from bats in South Kazakhstan, nucleotide sequences of putative novel bat adenovirus (AdV) species were found. Estimates of amino acid identities of the hexon protein have shown that potentially novel Bat mastadenovirus BatAdV-KZ01 shared higher similarity with monkey Rhesus adenovirus 59 (74.29%) than with Bat AdVs E and H (74.00%). Phylogenetically, BatAdV-KZ01 formed a separate clade, distant from Bat AdVs and other mammalian AdVs. Since adenoviruses are essential pathogens for many mammals, including humans and bats, this finding is of interest from both scientific and epidemiological points of view.

Canine distemper virus and canine adenovirus type 1 co-infection in a free-living hoary fox (Lycalopex vetulus) from Brazil.

The present case is the first description of a co-infection with canine distemper virus (CDV) and canine adenovirus type 1 (CAdV-1) in a free-living hoary fox pup from Brazil. The animal was found and rescued with poor body condition, dehydration, incoordination, ataxia, excessive vocalization, and "blue eyes" phenomenon. Despite the efforts, euthanasia was elected due to worsening clinical signs and poor prognosis. Pathologic examination revealed a mild, acute, random, necrotizing hepatitis, acute bronchopneumonia, hydrocephalus, corneal edema with epithelium degeneration, and acidophilic intracytoplasmatic inclusion bodies in different epithelial cells types with rare syncytial. Through immunohistochemistry, CDV antigen was observed in the tongue, trachea, lungs, liver, spleen, stomach, intestine and urinary bladder. Adenovirus antigen was identified in the nucleus of scattered hepatocytes. Polymerase chain reaction and sequencing demonstrated high similarity with CAdV-1 and wild-type strain of CDV close related to Brazilian viral lineages isolated from domestic dogs. Disease surveillance in wildlife animals is essential to assess possible conservation threats and consider the implementation of mitigation or control measures.

Genetic diversity of adenovirus in neotropical bats from Brazil

Bats can harbor a diversity of viruses, such as adenovirus. Ten different species of bat adenoviruses (BtAdV A to J) have been previous described worlwide. In Brazil, BtAdV was described in three species of phyllostomid species: Artibeus lituratus, Desmodus rotundus, and Sturnira lilium. There are around 180 bat species in Brazil, with 67% inhabiting the Atlantic Forest, with few information about the circulation of BtAdV in this biome. We aimed to describe the molecular detection and the phylogenetic characterization and suggest a classification of BtAdVs circulating in bats from the Brazilian Atlantic Forest. We collected 382 oral and rectal swabs from 208 bats between 2014–2015 and 2020–2021 from São Paulo, Pernambuco, and Santa Catarina Brazilian states. The adenovirus detection was done by a nested PCR targeting the DNA polymerase gene, and all positive samples were sequenced by the Sanger method. The phylogenetic analyses were based on the amino acid sequences using the MEGA 7 and BEAST software. We obtained 16 positive animals (detection rate 7.7%) belonging to seven bat species: Artibeus lituratus, Carollia perspicillata, Sturnira lilium, Molossus molossus, and the first record of Phyllostomus discolor, Eptesicus diminutus, and Myotis riparius. The phylogenetic analysis based on partial amino acid sequences showed that all obtained AdV sequences belong to the Mastadenovirus genus. We observed a high genetic diversity of BtAdV and identified eleven potential BtAdV species circulating in Brazil (BtAdV K to U). Our results contribute to the epidemiological surveillance of adenovirus, increasing the knowledge about the viral diversity and the distribution of AdV in bats from the Atlantic Forest.

Multi-omic interactions in the gut of children at the onset of islet autoimmunity.

BACKGROUND: The gastrointestinal ecosystem is a highly complex environment with a profound influence on human health. Inflammation in the gut, linked to an altered gut microbiome, has been associated with the development of multiple human conditions including type 1 diabetes (T1D). Viruses infecting the gastrointestinal tract, especially enteroviruses, are also thought to play an important role in T1D pathogenesis possibly via overlapping mechanisms. However, it is not known whether the microbiome and virome act together or which risk factor may be of greater importance at the time when islet autoimmunity is initiated. RESULTS: Here, we apply an integrative approach to combine comprehensive fecal virome, microbiome, and metaproteome data sampled before and at the onset of islet autoimmunity in 40 children at increased risk of T1D. We show strong age-related effects, with microbial and metaproteome diversity increasing with age while host antibody number and abundance declined with age. Mastadenovirus, which has been associated with a reduced risk of T1D, was associated with profound changes in the metaproteome indicating a functional shift in the microbiota. Multi-omic factor analysis modeling revealed a cluster of proteins associated with carbohydrate transport from the genus Faecalibacterium were associated with islet autoimmunity. CONCLUSIONS: These findings demonstrate the interrelatedness of the gut microbiota, metaproteome and virome in young children. We show a functional remodeling of the gut microbiota accompanies both islet autoimmunity and viral infection with a switch in function in Faecalibacterium occurring at the onset of islet autoimmunity. Video Abstract.

Study on the Canine Adenovirus Type 1 (CAdV-1) Infection in Domestic Dogs in Southern Italy.

Canine adenovirus type 1 (CAdV-1) is the causative agent of a systemic and potentially fatal viral disease of domestic and wild canids. In Italy, CAdV-1 infection has also been occasionally described in dogs, but information on the epidemiology and its genomic features is still limited. A study was conducted on 291 dogs suspected of infectious gastrointestinal disease. Samples collected from dogs in southern Italy between 2017 and 2020 were analyzed. Virological and histopathological assays were carried out. The presence of CAdVs and other canine viral enteropathogens was investigated, and sequence and phylogenetic analyses were performed. CAdV-1 was detected in six (2.1%) dead stray dogs alone or in mixed infections with other viruses. Gross lesions and histopathological findings referred to CAdV infection were observed, also involving the central nervous system tissues. All inoculated samples were successfully isolated. Sequence analysis evidenced divergences with the circulating strains previously described in Italy and a closer relation with older CAdV-1 strains collected from other countries, suggesting a genetic heterogeneity of CAdV-1 in Italy. The evidence of the circulation of CAdV-1 and its genomic features allows us to have more in-depth knowledge of the epidemiology and evolution of the CAdV-1 genomic variants.

High Rates of Detection and Molecular Characterization of Porcine Adenovirus Serotype 5 (Porcine mastadenovirus C) from Diarrheic Pigs.

Since the first report on isolation of porcine adenovirus serotype 5 (PAdV-5, species Porcine mastadenovirus C (PAdV-C)) from pigs with respiratory illness in Japan in 1987, PAdV-5 have been detected in a few fecal samples from healthy pigs and in some environmental samples. To date, only a single PAdV-5 strain (isolate HNF-70 from 1987) has been analyzed for the complete genome. We report here high detection rates of PAdV-5 (25.74%, 26/101 fecal samples) in diarrheic pigs at 3 different farms in the Caribbean country of Dominican Republic. After a long gap, the complete deduced amino acid sequences of the DNA-dependent DNA polymerase (pol) and hexon of two PAdV-5 strains (GES7 and Z11) were determined, revealing >99% sequence identities between PAdV-5 strains (HNF-70, GES7 and Z11) detected in different parts of the world and during different time periods (1987, and 2020−2021). By phylogenetic analysis, the putative hexon and pol of HNF-70, GES7 and Z11 exhibited similar clustering patterns, with the PAdV-5 strains forming a tight cluster near ruminant AdVs, distinct from the species PAdV-A and -B. GES7 and Z11 retained the various conserved features present in the putative pol and major late promoter region of HNF-70. Considering the paucity of data on current epidemiological status and genetic diversity of PAdV in porcine populations, our findings warrant similar studies on PAdV-5 and other PAdVs in clinically ill and healthy pigs. To our knowledge, this is the first report on detection and molecular characterization of PAdV-5 (PAdV-C) from diarrheic pigs.

Genome Analyses of Ten New Ape Adenoviruses with Similarity to Human Mastadenovirus C.

The adenoviruses (AdVs) isolated from humans are taxonomically grouped in seven different species in the Mastadenovirus genus (HAdV-A through G). AdVs isolated from apes are often included in one of the human AdV species. Here we describe the sequence analyses of ten new AdVs that are related to the HAdV-C species and that were isolated from healthy western lowland gorillas, bonobos, chimpanzees, and orangutans kept in Dutch zoos. We analyzed these viruses and compared their genome sequences to those of human- and ape-derived AdV sequences in the NCBI GenBank database. Our data demonstrated that the ape-derived viruses clustering to HAdV-C are markedly distinct from the human HAdV-C species in the size and nucleotide composition (%GC) of their genome, differ in the amino-acid sequence of AdV proteins, and have longer RGD-loops in their penton-base proteins. The viruses form three well-separated clades (the human, the gorilla, and the combined group of the bonobo and chimpanzee viruses), and we propose that these should each be given species-level ranks. The Ad-lumc005 AdV isolated from orangutans was found to be very similar to the gorilla AdVs, and bootstrap inference provided evidence of recombination between the orangutan AdV and the gorilla AdVs. This suggests that this virus may not be a genuine orangutan AdV but may have been transferred from a gorilla to an orangutan host.

Human Mastadenovirus Infections in Children: A Review of the Current Status in the Arab World in the Middle East and North Africa.

Human mastadenovirus (HAdV) is a non-enveloped icosahedral virus with double-stranded DNA genomes. The mortality rate of HAdV infections can reach 35.5%, while gastroenteritis HAdV infections, HAdV pneumonia, and disseminated disease tend to show a worse outcome, with rates ranging from 44.2% to 50%. In addition, HAdV can cause infections at any age but most commonly in the pediatric population, especially in young children and infants. Therefore, this review aims to assess the current status of HAdV infections among children in the Arab World, particularly in the Middle East and North Africa. Web of Science, Scopus, PubMed, EMBASE, and Google Scholar databases for publications in English were searched up to July 2022 for relevant articles. The literature search yielded a total of 21 studies, which were included in this review. Studies reporting HAdV infections in children were conducted in 17 out of the 22 countries. The average prevalence rate of HAdV infections in children was 12.7%, with average prevalence rates of 12.82% and 12.58% in the Middle East and North African countries, respectively. The highest prevalence rate (28.3%) was reported in Egypt, whereas the lowest prevalence (1.5%) was reported in Sudan. The included studies presented children with signs and symptoms of gastroenteritis, acute respiratory infection, acute diarrhea, and acute hemorrhagic conjunctivitis. In conclusion, the average prevalence rate of HAdV infections in children was 12.7%, with average prevalence rates of 12.82% and 12.58% in the Middle East and North African countries, respectively. Finding the precise prevalence rate of this virus is crucial because it will guide future planning for effective disease control and the selection of particular treatment options during epidemics and special seasons.

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.

Host diversification is concurrent with linear motif evolution in a Mastadenovirus hub protein.

Over one hundred Mastadenovirus types infect seven orders of mammals. Virus-host coevolution may involve cospeciation, duplication, host switch and partial extinction events. We reconstruct Mastadenovirus diversification, finding that while cospeciation is dominant, the other three events are also common in Mastadenovirus evolution. Linear motifs are fast-evolving protein functional elements and key mediators of virus-host interactions, thus likely to partake in adaptive viral evolution. We study the evolution of eleven linear motifs in the Mastadenovirus E1A protein, a hub of virus-host protein-protein interactions, in the context of host diversification. The reconstruction of linear motif gain and loss events shows fast linear motif turnover, corresponding a virus-host protein-protein interaction turnover orders of magnitude faster than in model host proteomes. Evolution of E1A linear motifs is coupled, indicating functional coordination at the protein scale, yet presents motif-specific patterns suggestive of convergent evolution. We report a pervasive association between Mastadenovirus host diversification events and the evolution of E1A linear motifs. Eight of 17 host switches associate with the gain of one linear motif and the loss of four different linear motifs, while five of nine partial extinctions associate with the loss of one linear motif. The specific changes in E1A linear motifs during a host switch or a partial extinction suggest that changes in the host molecular environment lead to modulation of the interactions with the retinoblastoma protein and host transcriptional regulators. Altogether, changes in the linear motif repertoire of a viral hub protein are associated with adaptive evolution events during Mastadenovirus evolution.

Sensitivity of Human Mastadenovirus, the Causal Agent of Pharyngoconjunctival Fever, Epidemic Keratoconjunctivitis, and Hemorrhagic Cystitis in Immunocompromised Individuals, to Brincidofovir.

Human mastadenovirus (HAdV), a linear double-stranded DNA (dsDNA) virus, is the causal agent of several diseases, including pharyngoconjunctival fever, epidemic keratoconjunctivitis, and hemorrhagic cystitis, in immunocompromised individuals. There are more than 100 reported types of adenoviruses, but the pathogenicity of many HAdVs remains unknown. Brincidofovir (BCV) is a hexadecyloxypropyl lipid conjugate of cidofovir (CDV) that is active against dsDNA viruses. Clinical effectiveness of BCV against certain HAdV species has been reported; however, its activity against novel HAdV types remains unknown. We investigated the half-maximal inhibitory concentration (IC50) values of BCV for novel HAdV types and found that the epidemic keratoconjunctivitis-associated HAdV-D54 prevalent in the Asian region was the most susceptible. The mean overall IC50 value of BCV was lower than that of CDV, indicating that BCV is effective against HAdVs, including the novel types. IMPORTANCE We investigated the IC50 values of BCV for novel HAdV types and found that the epidemic keratoconjunctivitis-associated HAdV-D54 prevalent in the Asian region was the most susceptible. In addition, the mean overall IC50 value of BCV was lower than that of CDV, indicating that BCV is effective against HAdVs.