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Balazs Harrach - One of the best experts on this subject based on the ideXlab platform.

  • Isolation and complete genome sequence analysis of a novel ovine adenovirus type representing a possible new Mastadenovirus species
    Archives of Virology, 2019
    Co-Authors: Márton Z. Vidovszky, Balazs Harrach, Levente Szeredi, Andor Doszpoly, Ákos Hornyák
    Abstract:

    Pathological examination of a suckling male lamb showed severe viral pneumonia with suspected bacterial superinfection. Adenovirus was detected by immunohistochemical examination of the affected lung samples. Detection of the suspected adenovirus by PCR and subsequent isolation of the virus were successful. Using next-generation sequencing, the full genome of this ovine adenovirus was sequenced and analysed. A genome sequence comparison showed that it was a novel Mastadenovirus type (named “ovine adenovirus 8”) that did not belong to any of the established adenovirus species. The genome is 36,206 bp long, containing 93-bp inverted terminal repeats and 29 predicted genes, including the two genus-specific genes (encoding proteins V and IX). Ovine adenovirus 8 shows the closest relationship to ovine adenovirus 6. These two viruses seem to merit the establishment of a novel ovine Mastadenovirus species for them, for which we proposed the name “ Ovine Mastadenovirus C ”.

  • polysialic acid is a cellular receptor for human adenovirus 52
    Proceedings of the National Academy of Sciences of the United States of America, 2018
    Co-Authors: Annasara Lenman, Balazs Harrach, Manuel A Liaci, Yan Liu, Lars Frangsmyr, Martin Frank, Barbel S Blaum, Wengang Chai, Iva I Podgorski, Maria Benkő
    Abstract:

    Human adenovirus 52 (HAdV-52) is one of only three known HAdVs equipped with both a long and a short fiber protein. While the long fiber binds to the coxsackie and adenovirus receptor, the function of the short fiber in the virus life cycle is poorly understood. Here, we show, by glycan microarray analysis and cellular studies, that the short fiber knob (SFK) of HAdV-52 recognizes long chains of α-2,8-linked polysialic acid (polySia), a large posttranslational modification of selected carrier proteins, and that HAdV-52 can use polySia as a receptor on target cells. X-ray crystallography, NMR, molecular dynamics simulation, and structure-guided mutagenesis of the SFK reveal that the nonreducing, terminal sialic acid of polySia engages the protein with direct contacts, and that specificity for polySia is achieved through subtle, transient electrostatic interactions with additional sialic acid residues. In this study, we present a previously unrecognized role for polySia as a cellular receptor for a human viral pathogen. Our detailed analysis of the determinants of specificity for this interaction has general implications for protein–carbohydrate interactions, particularly concerning highly charged glycan structures, and provides interesting dimensions on the biology and evolution of members of Human Mastadenovirus G.

  • Crystal structure of the fibre head domain of bovine adenovirus 4, a ruminant atadenovirus.
    Virology Journal, 2015
    Co-Authors: Thanh H. Nguyen, Balazs Harrach, Mónika Z. Ballmann, Maria Benkő, Márton Z. Vidovszky, Marta Sanz-gaitero, Abhimanyu K. Singh, Mark J. Van Raaij
    Abstract:

    Background In adenoviruses, primary host cell recognition is generally performed by the head domains of their homo-trimeric fibre proteins. This first interaction is reversible. A secondary, irreversible interaction subsequently takes place via other adenovirus capsid proteins and leads to a productive infection. Although many fibre head structures are known for human Mastadenoviruses, not many animal adenovirus fibre head structures have been determined, especially not from those belonging to adenovirus genera other than Mastadenovirus.

  • analysis of the first complete genome sequence of an old world monkey adenovirus reveals a lineage distinct from the six human adenovirus species
    Journal of General Virology, 2004
    Co-Authors: Gabor M Kovacs, Andrew J. Davison, Alexender N Zakhartchouk, Balazs Harrach
    Abstract:

    Simian adenovirus 3 (SAdV-3) is one of several adenoviruses that were isolated decades ago from Old World monkeys. Determination of the complete DNA sequence of SAdV-3 permitted the first full genomic comparison of a monkey adenovirus with adenoviruses of humans (HAdVs) and chimpanzees, which are recognized formally as constituting six of the species (HAdV-A to HAdV-F) within the genus Mastadenovirus. The SAdV-3 genome is 34 246 bp in size and has a G+C content of 55·3 mol%. It contains all the genes that are characteristic of the genus Mastadenovirus and has a single VA-RNA gene and six genes in each of the E3 and E4 regions. The genetic organization is the same as that of HAdV-12, a member of the HAdV-A species. Phylogenetic analyses showed that although SAdV-3 is related marginally more closely to HAdV-A and HAdV-F than to other species, it represents a unique lineage that branched at an early stage of primate adenovirus divergence. The results imply that the genetic layout in SAdV-3 and HAdV-12 may also have characterized the common ancestor of all sequenced primate adenoviruses.

  • four new inverted terminal repeat sequences from bovine adenoviruses reveal striking differences in the length and content of the itrs
    Virus Genes, 2001
    Co-Authors: Balazs Harrach, Zoltan Zadori, Maria Benkő
    Abstract:

    The inverted terminal repeat (ITR) of the genome of four bovine adenovirus (BAdV) types have been sequenced, analysed and compared to the ITRs of other adenoviruses. The length of ITRs of the examined BAdVs ranged between 59 and 368 base pairs, thus the presently known longest adenovirus ITR sequence is from BAdV-10. The conserved motifs and characteristic sequence elements of the ITRs providing different binding sites for replicative proteins of viral and cellular origin seemed to be distributed according to the proposed genus classification of BAdVs. The ITRs of BAdV-10 share similarity with the members of the genus Mastadenovirus, while the ITRs of the other three sequenced serotypes (BAdV-4, 5 and strain Rus) which are candidate members of the genus Atadenovirus are very short and contain NFI and Sp1 binding sites only. The analysis of the new ITRs implied that the nucleotide sequence of the so-called core origin is highly preserved within the Mastadenovirus genus only.

Adriana E Kajon - One of the best experts on this subject based on the ideXlab platform.

  • human Mastadenovirus b hadv b specific e3 cr1β and e3 cr1γ glycoproteins interact with each other and localize at the plasma membrane of non polarized airway epithelial cells
    Virology, 2020
    Co-Authors: Poornima Kotha Lakshmi Narayan, Adriana E Kajon
    Abstract:

    Abstract The E3 region of all simian and human types classified within species Human Mastadenovirus B (HAdV-B) encodes two unique highly conserved ORFs of unknown function designated E3-CR1β and E3-CR1γ. We generated a HAdV-3 mutant encoding small epitope tags at the N-termini of both E3-CR1β and E3-CR1γ (HAdV-3 N-tag wt) and a double knock out (HAdV-3 N-tag DKO) mutant virus that does not express either protein. Our studies show that HAdV-3 E3-CR1β and E3-CR1γ are type I transmembrane proteins that are produced predominantly at late times post infection, are glycosylated, co-localize at the plasma membrane of non-polarized epithelial cells, and interact with each other. At their extreme C-termini HAdV-B E3-CR1β and E3-CR1γ possess a conserved di-leucine motif followed by a class II PDZ domain binding motif (PBM). HAdV-3 E3-CR1β and E3-CR1γ are dispensable for virus growth, progeny release, spread, and plaque formation in A549 cells.

  • isolation of a novel intertypic recombinant human Mastadenovirus b2 from two unrelated bone marrow transplant recipients
    new microbes and new infections, 2020
    Co-Authors: Adriana E Kajon, Daryl M Lamson, E Spiridakis, A M Cardenas, N E Babady, Brian T Fisher, K St George
    Abstract:

    Human adenoviruses (HAdV) are well-known opportunistic pathogens of immunocompromised adult and pediatric patients but specific associations between HAdV species or individual HAdV types and disease are poorly understood. In this study we report the isolation of a novel HAdV-B2 genotype from two unrelated immunocompromised patients, both recipients of a hematopoietic cell transplant. In both patients, the course of HAdV infection is consistent with a scenario of reactivation of a latent virus rather than a primary opportunistic infection. Archived HAdV PCR-positive plasma, urine, and stool specimens were processed for virus isolation and detailed molecular characterization. Virus isolates were recovered from patient 1 from PCR-positive urine specimens obtained at days 103 and 116 after transplant in association with gross hematuria, and from a stool specimen obtained 138 days after transplant in association with diarrhea. An isolate was recovered from patient 2 from a PCR-positive urine specimen. Hexon and fiber gene amplification and sequencing were carried out for initial molecular typing, identifying the isolates as an intertypic recombinant with a HAdV-11-like hexon gene and a HAdV-77-like fiber gene. Comprehensive restriction fragment length polymorphism (RFLP) analysis was performed on viral DNA purified from urine and stool isolates, and next generation whole genome sequencing was carried out on purified viral genomic DNA. The genomes of the two isolated strains are 99.5% identical and represent the same RFLP genomic variant. The identified virus is a novel HAdV-B2 genotype designated HAdV-78 exhibiting a HAdV-11-like penton base, a HAdV-11-like hexon and a HAdV-77-like fiber (P11H11F77).

  • genomic characterization of human adenovirus type 4 strains isolated worldwide since 1953 identifies two separable phylogroups evolving at different rates from their most recent common ancestor
    Virology, 2019
    Co-Authors: Gabriel Gonzalez, Camden R Bair, Daryl M Lamson, Hidemi Watanabe, Laura Panto, Michael J Carr, Adriana E Kajon
    Abstract:

    Abstract Species Human Mastadenovirus E (HAdV-E) comprises several simian types and a single human type: HAdV-E4, a respiratory and ocular pathogen. RFLP analysis for the characterization of intratypic genetic variability has previously distinguished two HAdV-E4 clusters: prototype (p)-like and a-like. Our analysis of whole genome sequences confirmed two distinct lineages, which we refer to as phylogroups (PGs). PGs I and II comprise the p- and a-like genomes, respectively, and differ significantly in their G + C content (57.7% ± 0.013 vs 56.3% ± 0.015). Sequence differences distinguishing the two clades map to several regions of the genome including E3 and ITR. Bayesian analyses showed that the two phylogroups diverged approximately 602 years before the present. A relatively faster evolutionary rate was identified for PG II. Our data provide a rationale for the incorporation of phylogroup identity to HAdV-E4 strain designation to reflect the identified unique genetic characteristics that distinguish PGs I and II.

  • isolation and initial propagation of guinea pig adenovirus gpadv in cavia porcellus cell lines
    F1000Research, 2019
    Co-Authors: Adriana E Kajon, Gabriel Gonzalez, Susan Core, Helga Hofmannsieber, Shuguang Leng
    Abstract:

    Background:  The lack of adequate in vitro systems to isolate and propagate guinea pig adenovirus (GPAdV), a prevalent cause of respiratory illness of varaible severity in laboratory guinea pig colonies worldwide, has precluded its formal characterization to allow for the development of comprehensive diagnostic assays, and for the execution of complex pathogenesis and basic virology studies. Methods: Two strains of GPAdV were isolated in guinea pig ( Cavia porcellus ) cell cultures from frozen archival infected animal tissue originated from colony outbreaks of pneumonia in Australia and the Czech Republic in 1996. Results: Commercially available guinea pig cell lines from colorectal carcinoma (GPC-16), fetal fibroblast (104-C1) and lung fibroblast (JH4 C1), and the tracheal epithelial cell line GPTEC-T developed in this study were able to support viral infection and early propagation. Sufficient viral DNA was recovered from cell cultures to PCR-amplify and obtain sequence data for the complete hexon gene and partial DNA polymerase and penton base genes. Phylogenetic analysis for the three regions of the genome provided strong evidence confirming GPAdV as a unique species in the genus Mastadenovirus. Conclusions: This study demonstrated the feasibility of propagating GPAdV in cultures of immortalized lines of GP cells of a variety of types, thus establishing a critical foundation for the development of a robust culture platform for virus stock production and titration. The generation and analysis of whole GPAdV genome sequences will provide additional data for a comprehensive description of the genetic organization of the viral genome and for a better assessment of genetic diversity between the two isolated strains.

  • the complete genome sequence of human adenovirus 84 a highly recombinant new human Mastadenovirus d type with a unique fiber gene
    Virus Research, 2017
    Co-Authors: Győző L Kajan, Adriana E Kajon, Alexis Castillo Pinto, Daniel Bartha, Niklas Arnberg
    Abstract:

    A novel human adenovirus was isolated from a pediatric case of acute respiratory disease in Panama City, Panama in 2011. The clinical isolate was initially identified as an intertypic recombinant based on hexon and fiber gene sequencing. Based on the analysis of its complete genome sequence, the novel complex recombinant Human Mastadenovirus D (HAdV-D) strain was classified into a new HAdV type: HAdV-84, and it was designated Adenovirus D human/PAN/P309886/2011/84[P43H17F84]. HAdV-D types possess usually an ocular or gastrointestinal tropism, and respiratory association is scarcely reported. The virus has a novel fiber type, most closely related to, but still clearly distant from that of HAdV-36. The predicted fiber is hypothesised to bind sialic acid with lower affinity compared to HAdV-37. Bioinformatic analysis of the complete genomic sequence of HAdV-84 revealed multiple homologous recombination events and provided deeper insight into HAdV evolution.

Győző L Kajan - One of the best experts on this subject based on the ideXlab platform.

Niklas Arnberg - One of the best experts on this subject based on the ideXlab platform.

Ákos Hornyák - One of the best experts on this subject based on the ideXlab platform.

  • complete genome analysis confirms that the pygmy marmoset adenovirus is a variant of the skunk adenovirus 1 short communication
    Acta Veterinaria Hungarica, 2020
    Co-Authors: Andor Doszpoly, Ákos Hornyák, Krisztian Banyai
    Abstract:

    The complete genomic sequence along with phylogenetic analyses of an adenovirus (AdV), isolated from a dead captive pygmy marmoset (Callithrix pygmaea) from a Hungarian zoo is reported. Earlier, based on the phylogenetic analysis of the sequence of a PCR-amplified fragment from the DNA polymerase gene, the pygmy marmoset AdV (PMAdV) has been reported to cluster closest to certain chiropteran AdVs. In the following years similar AdVs were discovered in additional mammalian hosts, including a skunk (Mephitis mephitis), African pygmy hedgehogs (Atelerix albiventris), North American porcupines (Erethizon dorsatum) and grey fox (Urocyon cinereoargenteus). After the full genome analysis of the skunk adenovirus (SkAdV-1), a novel species Skunk Mastadenovirus A (SkAdV-A) has been established. The AdVs, originating from the African pygmy hedgehogs, have been found to belong to virus species SkAdV-A. Partial gene sequences from the porcupine AdVs have also implied their very close genetic relatedness to SkAdV-A. The complete genomic sequence of PMAdV, examined in this study, was found to share 99.83% nucleotide identity with SkAdV-1, thus unequivocally represents a genomic variant of SkAdV-1. The observation that viruses classifiable as SkAdV-A are able to infect and cause diseases in several, distantly related mammals seems to deserve further studies to elucidate the infection biology of this intriguing AdV.

  • Isolation and complete genome sequence analysis of a novel ovine adenovirus type representing a possible new Mastadenovirus species
    Archives of Virology, 2019
    Co-Authors: Márton Z. Vidovszky, Balazs Harrach, Levente Szeredi, Andor Doszpoly, Ákos Hornyák
    Abstract:

    Pathological examination of a suckling male lamb showed severe viral pneumonia with suspected bacterial superinfection. Adenovirus was detected by immunohistochemical examination of the affected lung samples. Detection of the suspected adenovirus by PCR and subsequent isolation of the virus were successful. Using next-generation sequencing, the full genome of this ovine adenovirus was sequenced and analysed. A genome sequence comparison showed that it was a novel Mastadenovirus type (named “ovine adenovirus 8”) that did not belong to any of the established adenovirus species. The genome is 36,206 bp long, containing 93-bp inverted terminal repeats and 29 predicted genes, including the two genus-specific genes (encoding proteins V and IX). Ovine adenovirus 8 shows the closest relationship to ovine adenovirus 6. These two viruses seem to merit the establishment of a novel ovine Mastadenovirus species for them, for which we proposed the name “ Ovine Mastadenovirus C ”.

  • novel Mastadenovirus infection and clinical disease in a pygmy marmoset callithrix cebuella pygmaea
    Veterinary Microbiology, 2013
    Co-Authors: Janos Gal, Levente Szeredi, Ákos Hornyák, Mira Mandoki, Tamas Bakonyi, Gyula Balka, Miklos Marosan, Tibor Ludanyi, Petra Forgach, Endre Sos
    Abstract:

    We describe the detection and successful isolation of a novel Mastadenovirus from a pygmy marmoset (Callithrix [Cebuella] pygmaea) that died following an episode of severe respiratory signs. Pathologic/histopathologic examination revealed hydrothorax and catarrhal bronchopneumonia with pronounced desquamation of the bronchiolar epithelial cells, while in other airways a marked hyperplasia of the epithelial lining and numerous giant cells could be observed. We obtained partial sequence data from the adenoviral DNA-dependent DNA-polymerase gene of the isolated strain and analyses of this region showed the highest level of identity to the recently described bat adenoviruses (strains PPV1 and TJM) and the type 2 canine adenovirus. Similar results were gained by phylogenetic calculations indicating that this novel marmoset adenovirus is only distantly related to reference Old and New World primate adenoviruses and formed a monophyletic group with bat and canine adenoviruses and the equine adenovirus 1. Even though the source of the infection remained unknown, our results could imply the possibility of a cross-species transmission of the virus from an anonymous host to the pygmy marmoset.