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Virology
Academic Press
Virology

Academic Press

0042-6822

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    An Adenovirus early region 4 deletion mutant induces G2/M arrest via ATM activation and reduces expression of the mitotic marker phosphorylated (ser10) histone 3

    Kafle, Chandra ManiAnderson, Ashlyn Y.Prakash, AnandSwedik, Stephanie...
    12页
    查看更多>>摘要：Adenovirus (Ad) type 5 (Ad5) early region 4 (E4) proteins inhibit the DNA damage response (DDR) including activation of the DDR kinase ATM and its substrates, which can induce G2/M cell cycle arrest. Infection with Ad5 or the E4 deletion mutant H5dl1007 (1007) resulted in the accumulation of post G1 cells with > 2 N cellular DNA content. A greater fraction of cells with 4 N DNA content was observed in 1007 infections compared to Ad5; this population was dependent on activation of ATM. G2/M checkpoint kinases, phosphorylated Chk2 (pChk2), and phosphorylated Cdk1 (pCdk1) were upregulated in 1007 infections, and 1007 showed reduced levels of the mitosis marker phosphorylated (Ser10) histone 3 compared to Ad5. Our results show that E4 mutant activation of ATM induces G2/M arrest via activation of checkpoint kinases, thereby contributing to viral-mediated regulation of the cell cycle.
      原文链接:
    • NSTL
    • Elsevier

    Exposing cryptic epitopes on the Venezuelan equine encephalitis virus E1 glycoprotein prior to treatment with alphavirus cross-reactive monoclonal antibody allows blockage of replication early in infection

    Calvert, Amanda E.Bennett, Susan L.Hunt, Ann R.Fong, Rachel H....
    9页
    查看更多>>摘要：Eastern equine encephalitis virus (EEEV), western equine encephalitis virus (WEEV) and Venezuelan equine encephalitis virus (VEEV) can cause fatal encephalitis in humans and equids. Some MAbs to the E1 glycopmtein are known to be cross-reactive, weakly neutralizing in vitro but can protect from disease in animal models. We investigated the mechanism of neutralization of VEEV infection by the broadly cross-reactive E1-specific MAb 1A4B-6. 1A4B-6 protected 3-week-old Swiss Webster mice prophylactically from lethal VEEV challenge. Likewise, 1A4B-6 inhibited virus growth in vitro at a pre-attachment step after virions were incubated at 37 degrees C and inhibited virus-mediated cell fusion. Amino acid residue N100 in the fusion loop of E1 protein was identified as critical for binding. The potential to elicit broadly cross-reactive MAbs with limited virus neutralizing activity in vitro but that can inhibit virus entry and protect animals from infection merits further exploration for vaccine and therapeutic developmental research.
      原文链接:
    • NSTL
    • Elsevier

    Structural characterization of an envelope-associated adeno-associated virus type 2 capsid

    Mietzsch, MarioChipman, PaulStrugatsky, DavidMcKenna, Robert...
    7页
    查看更多>>摘要：Adeno-associated virus (AAV) are classified as non-enveloped ssDNA viruses. However, AAV capsids embedded within exosomes have been observed, and it has been suggested that the AAV membrane associated accessory protein (MAAP) may play a role in envelope-associated AAV (EA-AAV) capsid formation. Here, we observed and selected sufficient homogeneous EA-AAV capsids of AAV2, produced using the Sf9 baculoviral expression system, to determine the cryo-electron microscopy (cryo-EM) structure at 3.14 angstrom resolution. The reconstructed map confirmed that the EA-AAV capsid, showed no significant structural variation compared to the non-envelope capsid. In addition, the Sf9 expression system used implies the notion that MAAP may enhance exosome AAV encapsulation. Furthermore, we speculate that these EA-AAV capsids may have therapeutic benefits over the currently used non-envelope AAV capsids, with advantages in immune evasion and/or improved infectivity.
      原文链接:
    • NSTL
    • Elsevier

    Dynamics of SARS-CoV-2 variants of concern (VOC) in Bangladesh during the first half of 2021

    Afrin, Sultana ZahuraIslam, Md TaohidulPaul, Shyamal KumarKobayashi, Nobumichi...
    9页
    查看更多>>摘要：Bangladesh is the second-worst-affected country in South Asia by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study is to examine genome sequences from Bangladesh from January 2021 to June 2021 in order to monitor the SARS-CoV-2 VOC and the clades or lineages that are prevalent in the country. Within the study timeframe, at least eight Nextstrain clades were found: 20A, 20B, 20C, 20H (Beta, V2), 20I (Alpha, V1), 20 J (Gamma, V3), 21A (Delta), 21D (Eta), and six GISAID clades: four main (G, GH, GR, GRY) and two minors (GV, O) with an introduction of VOC B.1.1.7/Alpha, B.1.351/Beta and B.1.617.2/Delta. The introduction and recent occurrence of VOCs with substantial alterations in the receptor binding site of spike protein (K417 N, K417T, L452R, T478K, E484K, S494P, N501Y) are of particular importance. Specifically, VOC B.1.617.2/Delta has surpassed all prior VOCs in Bangladesh, posing a challenge to the existing disease management.
      原文链接:
    • NSTL
    • Elsevier

    Diverse single-stranded DNA viruses identified in New Zealand (Aotearoa) South Island robin (Petroica australis) fecal samples

    Custer, Joy M.White, RobynTaylor, HelenSchmidlin, Kara...
    14页
    查看更多>>摘要：The South Island robin (Petroica australis) is a small passerine bird endemic to New Zealand (Aotearoa). Although its population has declined recently and it is considered 'at risk,' little research has been done to identify viruses in this species. This study aimed to survey the diversity of single-stranded DNA viruses associated with South Island robins in a small, isolated population on Nukuwaiata Island. In total, 108 DNA viruses were identified from pooled fecal samples collected from 38 individual robins sampled. These viruses belong to the Circoviridae (n = 10), Genomoviridae (n = 12), and Microviridae (n = 73) families. A number of genomes that belong to the phylum Cressdnaviricota but are otherwise unclassified (n = 13) were also identified. These results greatly expand the known viral diversity associated with South Island robins, and we identify a novel group of viruses most closely related genomoviruses.
      原文链接:
    • NSTL
    • Elsevier

    The local integration preference of the Tf1 retrotransposon in Schizosaccharomyces pombe

    Cui, YujinGuo, Yabin
    6页
    查看更多>>摘要：ABSTR A C T Transposons are mobile DNAs that can move to different locations in host genomes. The integration site selection of transposons is critical for both themselves and host cells. Studies on the integration of retrotransposons and retroviruses have focused more on the global preference than on the local preference. The local preferences of retrotransposons are usually weak and of large diversity. Here, we analyzed hundreds of thousands of inde-pendent integration events of the Tf1 retrotransposon in Schizosaccharomyces pombe. The consensus sequence at the Tf1 integration sites shows a palindromic pattern, which can be divided into four sections, each of them contains one or more CGnTA units with a period of 10 base pairs, indicating interaction with subunits of the integrase oligomer in the pre-integration complex. Moreover, the analysis on the nucleosome occupancy flanking Tf1 target sites shows that Tf1 integration favors regions with one entire nucleosome depletion.
      原文链接:
    • NSTL
    • Elsevier

    LDH nanoparticle adjuvant subunit vaccine induces an effective immune response for porcine epidemic diarrhea virus

    Shi, DanyiFan, BaochaoSun, BingZhou, Jinzhu...
    7页
    查看更多>>摘要：Porcine Epidemic Diarrhea (PED) is a highly contagious intestinal disease which mostly caused by Porcine Epidemic Diarrhea Virus (PEDV). The PED has caused huge economic losses to the pig industry all over the world and a valid PEDV vaccine is needed to prevent the infection. In this study, we constructed expression plasmid based on the spike (S) gene of the epidemic PEDV strain. The recombinant eukaryotic S (Se) and prokaryotic S (Sp) subunit proteins were expressed and purified as vaccine antigens. We designed a new subunit vaccine based on S proteins, adjuvanted with layered double hydroxide (LDH). The results indicated that the LDH adjuvanted subunit vaccines induced a better immune effect in terms of antibody level and cellular immune response. In conclusion, this study showed a new design of a PEDV subunit vaccine with nanotechnology and demonstrated the potential for its clinical application.
      原文链接:
    • NSTL
    • Elsevier

    Discovery of novel fish papillomaviruses: From the Antarctic to the commercial fish market

    Bradley, Russell W.Warzybok, PeteVan Doorslaer, KoenraadDavison, William...
    8页
    查看更多>>摘要：Fish papillomaviruses form a newly discovered group broadly recognized as the Secondpapillomavirinae sub-family. This study expands the documented genomes of the fish papillomaviruses from six to 16, including one from the Antarctic emerald notothen, seven from commercial market fishes, one from data mining of sea bream sequence data, and one from a western gull cloacal swab that is likely diet derived. The genomes of sec-ondpapillomaviruses are ~6 kilobasepairs (kb), which is substantially smaller than the ~8 kb of terrestrial vertebrate papillomaviruses. Each genome encodes a clear homolog of the four canonical papillomavirus genes, E1, E2, L1, and L2. In addition, we identified open reading frames (ORFs) with short linear peptide motifs reminiscent of E6/E7 oncoproteins. Fish papillomaviruses are extremely diverse and phylogenetically distant from other papillomaviruses suggesting a model in which terrestrial vertebrate-infecting papillomaviruses arose after an evolutionary bottleneck event, possibly during the water-to-land transition.
      原文链接:
    • NSTL
    • Elsevier

    BCG vaccination and the risk of COVID 19: A possible correlation

    Nasr, Mohamed A.Elshenawy, Shimaa E.Hussein, Alaa E.El-Betar, Ahmed H....
    9页
    查看更多>>摘要：Bacillus Calmette-Gue & PRIME;rin (BCG) vaccine is currently used to prevent tuberculosis infection. The vaccine was found to enhance resistance to certain types of infection including positive sense RNA viruses. The current COVID-19 pandemic is caused by positive sense RNA, severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). A higher mortality rate of COVID-19 patients was reported in countries where BCG vaccination is not routinely administered, when compared to the vaccinated ones. We hypothesized that BCG vaccine may control SARS-CoV2 infection via modulating the monocyte immune response. We analyzed GSE104149 dataset to investigate whether human monocytes of BCG-vaccinated individuals acquire resistance to SARS-CoV-2 infection. Differentially expressed genes obtained from the dataset were used to determine enriched pathways, biological processes, and molecular functions for monocytes post BCG vaccination. Our data show that BCG vaccine promotes a more effective immune response of monocytes against SARS-CoV2, but probably not sufficient to prevent the infection.
      原文链接:
    • NSTL
    • Elsevier

    DNA-PK phosphorylation at Ser2056 during adenovirus E4 mutant infection is promoted by viral DNA replication and independent of the MRN complex

    Chen, ChristopherBridge, Eileen
    14页
    查看更多>>摘要：Adenovirus (Ad) early region 4 (E4) mutants activate cellular DNA damage responses (DDRs) that include non-homologous end joining (NHEJ) pathways mediated by the DNA repair kinase DNA-PK and its associated factors Ku70/Ku86. NHEJ results in concatenation of the viral linear double-stranded DNA genome and inhibits a productive infection. E4 proteins normally prevent activation of cellular DDRs in wild-type Ad type 5 (Ad5) infections, thereby promoting efficient viral growth. The purpose of this study was to evaluate the factors that govern DNA-PK activation during adenovirus infection. Our data indicate that viral DNA replication promotes DNA-PK activation, which is required for genome concatenation by NHEJ. Although the Mre11/Rad50/Nbs1 (MRN) DDR sensor complex is not required for DNA-PK activation, Mre11 is important for recruitment of the NHEJ factor Ku86 to viral replication centers. Our study addresses the interplay between the DNA-PK and MRN complexes during viral genome concatenation by NHEJ.
      原文链接:
    • NSTL
    • Elsevier