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Dipendra Gautam, Gabrielle Stanley, Mary Owen, Eileen Bridge
Adenovirus (Ad) type 5 (Ad5) E4 deletion mutants including H5dl1007 (E4-) induce a DNA damage response (DDR) that activates the kinase ataxia-telangiectasia mutated (ATM), which can interfere with efficient viral DNA replication. We find that localization of active phosphorylated ATM (pATM) to E4- viral replication centers (VRCs) is important for its inhibitory effect. ATM is necessary for localization of RNF8 and 53BP1 to E4 mutant VRCs, while recruitment of DDR factors Mre11, Mdc1 and γH2AX is ATM-independent, raising the possibility that ATM may affect viral chromatin at VRCs...
November 16, 2018: Virology
Ying Wang, Zheng-You Yang, Yan-Ping Tian, Chao Geng, Xue-Feng Yuan, Xiang-Dong Li
To investigate the role of Tobacco vein banding mosaic virus (TVBMV) 3'-UTR in virus systemic infection, three types of deletions were introduced into TVBMV infectious clone pCaTVBMV-GFP. Mutants with deletions at the nucleotide position 8-42, 43-141, or 163-174 in the 3'-UTR failed to cause systemic infection in N. benthamiana plants. Other deletion mutants caused delayed systemic infection and milder vein clearing and mosaic symptoms. Most progeny mutant virus had acquired nucleotides, similar to or different from the deleted nucleotide sequences, after a single passage in the host plant...
November 16, 2018: Virology
Barbara Jester, Timothy M Uyeki, Daniel B Jernigan, Terrence M Tumpey
One hundred years have passed since the 1918 influenza pandemic caused substantial illness globally, with an estimated 50 million deaths. A number of factors, including World War I, contributed to the spread of the pandemic virus, which often caused high symptomatic attack rates and severe illness. Major achievements over the last 100 years have been made in influenza prevention, diagnosis, and treatment; however, the potential for a severe pandemic to emerge remains unchanged. We provide a review of the historical context and clinical aspects of illness due to the influenza A(H1N1) virus as it emerged and spread in 1918, with a focus on the experience in the United States...
November 16, 2018: Virology
Nazanin Mohammadzadeh, Tyson B Follack, Robin P Love, Kris Stewart, Stephen Sanche, Linda Chelico
The APOBEC3 enzyme family are host restriction factors that induce mutagenesis of HIV-1 proviral genomes through the deamination of cytosine to form uracil in nascent single-stranded (-)DNA. HIV-1 suppresses APOBEC3 activity through the HIV-1 protein Vif that induces APOBEC3 degradation. Here we compared two common polymorphisms of APOBEC3F. We found that although both polymorphisms have HIV-1 restriction activity, APOBEC3F 108 A/231V can restrict HIV-1 ΔVif up to 4-fold more than APOBEC3F 108 S/231I and is partially protected from Vif-mediated degradation...
November 15, 2018: Virology
Masamichi Isogai, Takanori Matsudaira, Makoto Ito, Nobuyuki Yoshikawa
A product translated from the 1b gene of raspberry bushy dwarf virus (RBDV) was specifically detected in RBDV-infected Nicotiana benthamiana plants by immunoblot analysis. To analyze the effects of the 1b gene on virus infection in host plants, an RBDV deletion mutant virus (RB∆1bstop), which is unable to express the 1b gene, was constructed and inoculated to N. benthamiana plants. The results showed that accumulation of the virus genomic (g) RNAs 1 and 2 decreased in inoculated leaves, and that systemic virus spread was delayed compared with wild-type RBDV...
November 14, 2018: Virology
Haiping Wang, Weifan Xu, Xiangshuo Kong, Ying Fan, Xiaofeng Wu
Bombyx mori nucleopolyhedrovirus (BmNPV) orf11 (bm11) is a highly conserved gene with unknown function. It is homologous to AcMNPV orf19. In this study, a bm11 knockout virus was constructed and its role was investigated. Expression analysis indicated that bm11 is a late gene and confocal microscopy analysis demonstrated that Bm11 localizes predominantly in the nuclear ring zone at the late phase of infection. The bm11 deletion did not affect budded virus (BV) production or viral genome replication, but markedly reduced the production of occlusion bodies (OBs) and the embedding of occlusion-derived viruses (ODVs)...
November 14, 2018: Virology
Jeffrey J Hodgson, Nicolas Buchon, Gary W Blissard
The baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is a model enveloped DNA virus that infects and replicates in lepidopteran insect cells, and can efficiently enter a wide variety of non-host cells. Budded virions of AcMNPV enter cells by endocytosis and traffic to the nucleus where the virus initiates gene expression and genome replication. While trafficking of nucleocapsids by actin propulsion has been studied in detail, other important components of trafficking during entry remain poorly understood...
November 13, 2018: Virology
Rasha E Shalaby, Saira Iram, Claudia E Oropeza, Alan McLachlan
Transcriptional coactivators represent critical components of the transcriptional pre-initiation complex and are required for efficient gene activation. Members of the peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) family differentially regulate hepatitis b virus (HBV) biosynthesis. Whereas PGC1α has been shown to be a potent activator of HBV biosynthesis, PGC1β only very poorly activates HBV RNA and DNA synthesis in human hepatoma (HepG2) and embryonic kidney (HEK293T) cells. Furthermore, PGC1β inhibits PGC1α-mediated HBV biosynthesis...
November 9, 2018: Virology
Jing Zhang, Li Zong, Yongxiang Wang, Cheng Li, Chaoyang Chen, Yumei Wen, Jisu Li, Shuping Tong
Hepatitis B virus genotype G possesses a 36-nucleotide (nt) insertion at the 5' end of core gene, adding 12 residues to core protein. The insertion markedly increased core protein level irrespective of viral genotype, with the effect reproducible using CMV-core gene construct. Here we used such expression constructs and transient transfection experiments in Huh7 cells to identify the structural bases. The insertion is predicted to create a stem-loop structure 14nt downstream of core gene AUG. A + 1 or + 2 frameshift into the 36nt mitigated enhancement of core protein level...
November 8, 2018: Virology
Hongru Li, Benjamin K Chen
HIV-1 transmission is usually initiated by a single viral strain called transmitted/ founder (T/F) virus. In in vitro models, HIV-1 can efficiently spread via cell-free and virological synapse (VS)-mediated cell-to-cell infection. Both modes of infection require the viral glycoprotein Envelope (Env). The efficiency with which T/F Envs initiate VS and mediate cell-to-cell infection has not been well characterized. Here we tested a panel of isogenic HIV-1 molecular clones that carry different Clade B T/F Envs...
November 8, 2018: Virology
Nigel Bourne, Brianne N Banasik, Clarice L Perry, Aaron L Miller, Mellodee White, Richard B Pyles, Gregg N Milligan
Most analyses of genital immunity to herpes simplex virus type 2 (HSV-2) have been performed in females, consequently immune protection of the male genital epithelium is incompletely understood. We developed a model of male genital HSV-2 infection resulting from intrarectal inoculation of guinea pigs. Vesicular lesions developed transiently on the perineum and foreskin concurrent with acute virus shedding. Virus shedding and recurrent genital lesions were also detected after establishment of a latent infection...
November 6, 2018: Virology
Aaron W Walters, Michael R Kujawa, Joseph R Albe, Douglas S Reed, William B Klimstra, Amy L Hartman
Rift Valley fever virus (RVFV) is a zoonotic disease of livestock that causes several clinical outcomes in people including febrile disease, hemorrhagic fever, and/or encephalitis. After aerosol infection with RVFV, Lewis rats develop lethal encephalitic disease, and we use this as a model for studying disease mechanisms of RVFV infection in the brain. Permeability of the brain vasculature in relation to virus invasion and replication is not known. Here, we found that vascular permeability in the brain occurred late in the course of infection and corresponded temporally to expression of matrix metalloproteinase-9 (MMP-9)...
November 2, 2018: Virology
Shaoyan Zhang, Rong Sun, Qin Guo, Xiao-Feng Zhang, Feng Qu
We recently reported that p28, one of the two turnip crinkle virus (TCV) replication proteins, trans-complemented a defective TCV lacking p28, yet repressed the replication of another TCV replicon encoding wild-type p28 (Zhang et al., 2017). Here we show that p88, the TCV-encoded RNA-dependent RNA polymerase, likewise trans-complemented a p88-defective TCV replicon, but repressed one encoding wild-type p88. Surprisingly, lowering p88 protein levels enhanced trans-complementation, but weakened repression. Repression by p88 was not simply due to protein over-expression, as deletion mutants missing 127 or 224 N-terminal amino acids accumulated to higher levels but were poor repressors...
November 1, 2018: Virology
Marlynne Q Nicol, Gillian M Campbell, Darren J Shaw, Ian Dransfield, Yvonne Ligertwood, Philippa M Beard, Anthony A Nash, Bernadette M Dutia
IFNγ is a key regulator of inflammatory responses but its role in influenza A virus (IAV) pathogenesis is unclear. Our studies show that infection of mice lacking the IFNγ receptor (IFNγR-/- ) at a dose which caused severe disease in wild type 129 Sv/Ev (WT) mice resulted in milder clinical symptoms and significantly lower lung virus titers by 6 days post-infection (dpi). Viral spread was reduced in IFNγR-/- lungs at 2 and 4 dpi. Levels of inflammatory cytokines and chemokines were lower in IFNγR-/- mice at 2 dpi and there was less infiltration of monocyte/macrophage lineage cells than in WT mice...
October 31, 2018: Virology
Brett L Hurst, W Joseph Evans, Donald F Smee, Arnaud J Van Wettere, E Bart Tarbet
Enterovirus D68 (EV-D68) is unique among enteroviruses because of the ability to cause severe respiratory disease as well as neurological disease. We developed separate models of respiratory and neurological disease following EV-D68 infection in AG129 mice that respond to antiviral treatment with guanidine. In four-week-old mice infected intranasally, EV-D68 replicates to high titers in lung tissue increasing the proinflammatory cytokines MCP-1 and IL-6. The respiratory infection also produces an acute viremia...
October 31, 2018: Virology
N Szerman, C Allée, E Lemaitre, C Courtillon, M Amelot, D Courtois, C Naylor, A Leroux, P Lucas, Y Blanchard, N Eterradossi, P A Brown
Subgroup C Avian Metapneumoviruses (AMPV-C) has two lineages, one mostly in turkeys and one mostly in ducks. To investigate the molecular basis of AMPV-C host tropism, a reverse genetics system for a duck AMPV-C virus was developed. A recombinant copy and a recombinant virus in which the SH protein had been exchanged for that of a turkey AMPV-C were rescued. No change in cytopathogenic effect or replication profile in vitro were observed for either virus compared to the wild type. In SPF Muscovy ducks the wild type and its recombinant copy were equally pathogenic...
October 30, 2018: Virology
Lijuan Yin, Li Chen, Yangyang Luo, Limiao Lin, Qunhui Li, Peng Peng, Yunping Du, Zhichao Xu, Chunyi Xue, Yongchang Cao, Qingfeng Zhou
As a novel duck adenovirus 3 (DAdV-3) infection caused significant economic losses to the poultry industry in China, there is an urgent need to develop a safe and effective vaccine. In the research, fiber-1 and fiber-2 proteins were expressed and purified, respectively. To evaluate the immunogenicity of the two recombinant proteins, we investigated the IgY antibodies and virus-neutralizing antibodies in duck sera. The protective efficacy was evaluated by mortality, virus shedding and histopathological examinations after challenged with the DAdV-3...
October 26, 2018: Virology
Shih-Chi Wang, Hsin-Yu Liao, Jia-Yan Zhang, Ting-Jen Rachel Cheng, Chi-Huey Wong
The development of a universal influenza vaccine has become a major effort to combat the high mutation rate of influenza. To explore the use of the highly conserved stem region of hemagglutinin (HA) as a universal vaccine, we produced HA-stem-based protein using yeast expression systems. The glycosylation effects on the immunogenicity and protection activities were investigated. The yield of the A/Brisbane/59/2007 HA stem produced from Pichia pastoris reached 100 mg/l. The immunogenicity of HA stem proteins in various glycoforms was further investigated and compared...
October 26, 2018: Virology
P Srilatha, Faisal Yousuf, Ramesh Methre, T Vishnukiran, Surekha Agarwal, Yugandhar Poli, M Raghurami Reddy, B Vidyasagar, Chitra Shanker, D Krishnaveni, S Triveni, Brajendra, Shelly Praveen, S M Balachandran, D Subrahmanyam, Satendra K Mangrauthia
Rice tungro disease is caused by the combined action of Rice tungro bacilliform virus (RTBV) and Rice tungro spherical virus (RTSV). The RTBV is involved in the development of symptoms while RTSV is essential for virus transmission. We attempted to study the mode of action of RTBV in the development of symptoms. The tungro disease symptoms were attributed to viral interference in chlorophyll and carotenoids biosynthesis, photosynthesis machinery, iron/zinc homeostasis, and the genes encoding the enzymes associated with these biological processes of rice...
October 26, 2018: Virology
Côme J Thieulent, Erika S Hue, Christine I Fortier, Patrick Dallemagne, Stéphan Zientara, Hélène Munier-Lehmann, Aymeric Hans, Guillaume D Fortier, Pierre-Hugues Pitel, Pierre-Olivier Vidalain, Stéphane L Pronost
Equid alpha-herpesviruses (EHV) are responsible for different diseases in equine population. EHV-1 causes respiratory diseases, abortions and nervous disorders, EHV-4 causes respiratory diseases and sporadic abortion, while EHV-3 is responsible of equine coital exanthema. In view of the lack of efficacy of vaccines against EHV-1 and EHV-4 and in the absence of vaccines against EHV-3, the use of antiviral treatment is of great interest. In this study, we documented the interest of the Real-Time Cell Analysis (RTCA) technology to monitor the cytopathic effects induced by these viruses on equine dermal cells, and established the efficacy of this method to evaluate the antiviral effect of aciclovir (ACV) and ganciclovir (GCV)...
October 26, 2018: Virology
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