Browsing by Subject "HEPATITIS-C VIRUS"

Sort by: Order: Results:

Now showing items 1-4 of 4
  • Phan, Tuan L.; Lautenschlager, Irmeli; Razonable, Raymund R.; Munoz, Flor M. (2018)
    Human herpesvirus 6 (HHV-6A and HHV-6B) can cause primary infection or reactivate from latency in liver transplant recipients, which can result in a variety of clinical syndromes, including fever, hepatitis, encephalitis and higher rates of graft dysfunction as well as indirect effects including increased risks of mortality, CMV disease, hepatitis C progression and greater fibrosis scores. Although HHV-6 infection is currently diagnosed by quantifying viral DNA in plasma or blood, biopsy to demonstrate histopathological effects of HHV-6 remains the gold standard for diagnosis of end-organ disease. HHV-6 reactivation may be restricted to the infected organ with no evidence of active infection in the blood. HHV-6 infections in liver transplant patients are mostly asymptomatic, but clinically significant tissue-invasive infections have been treated successfully with ganciclovir, foscarnet or cidofovir. Inherited chromosomally integrated HHV-6 (ciHHV-6), in either the recipient or the donor organ, may create confusion about systemic HHV-6 infection. Recipients with inherited ciHHV-6 may have an increased risk of opportunistic infection and graft rejection. This article reviews the current scientific data on the clinical effects, risk factors, pathogenesis, diagnosis and treatment of HHV-6 infections in liver transplant recipients.
  • Collier, Aaron M.; Lyytinen, Outi L.; Guo, Yusong R.; Toh, Yukimatsu; Poranen, Minna M.; Tao, Yizhi J. (2016)
    During the replication cycle of double-stranded (ds) RNA viruses, the viral RNA-dependent RNA polymerase (RdRP) replicates and transcribes the viral genome from within the viral capsid. How the RdRP molecules are packaged within the virion and how they function within the confines of an intact capsid are intriguing questions with answers that most likely vary across the different dsRNA virus families. In this study, we have determined a 2.4 angstrom resolution structure of an RdRP from the human picobirnavirus (hPBV). In addition to the conserved polymerase fold, the hPBV RdRP possesses a highly flexible 24 amino acid loop structure located near the C-terminus of the protein that is inserted into its active site. In vitro RNA polymerization assays and site-directed mutagenesis showed that: (1) the hPBV RdRP is fully active using both ssRNA and dsRNA templates; (2) the insertion loop likely functions as an assembly platform for the priming nucleotide to allow de novo initiation; (3) RNA transcription by the hPBV RdRP proceeds in a semi-conservative manner; and (4) the preference of virus-specific RNA during transcription is dictated by the lower melting temperature associated with the terminal sequences. Co-expression of the hPBV RdRP and the capsid protein (CP) indicated that, under the conditions used, the RdRP could not be incorporated into the recombinant capsids in the absence of the viral genome. Additionally, the hPBV RdRP exhibited higher affinity towards the conserved 5'-terminal sequence of the viral RNA, suggesting that the RdRP molecules may be encapsidated through their specific binding to the viral RNAs during assembly.
  • Ianevski, Aleksandr; Zusinaite, Eva; Kuivanen, Suvi; Strand, Mårten; Lysvand, Hilde; Teppor, Mona; Kakkola, Laura; Paavilainen, Henrik; Laajala, Mira; Kallio-Kokko, Hannimari; Valkonen, Miia; Kantele, Anu; Telling, Kaidi; Lutsar, Irja; Letjuka, Pille; Metelitsa, Natalja; Oksenych, Valentyn; Bjørås, Magnar; Nordbø, Svein Arne; Dumpis, Uga; Vitkauskiene, Astra; Öhrmalm, Christina; Bondeson, Kåre; Bergqvist, Anders; Aittokallio, Tero; Cox, Rebecca J.; Evander, Magnus; Hukkanen, Veijo; Marjomaki, Varpu; Julkunen, Ilkka; Vapalahti, Olli; Tenson, Tanel; Merits, Andres; Kainov, Denis (2018)
    Abstract According to the WHO, there is an urgent need for better control of viral diseases. Re-positioning existing safe-in-human antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we reviewed all approved, investigational and experimental antiviral agents, which are safe in man, and identified 59 compounds that target at least three viral diseases. We tested 55 of these compounds against eight different RNA and DNA viruses. We found novel activities for dalbavancin against echovirus 1, ezetimibe against human immunodeficiency virus 1 and Zika virus, as well as azacitidine, cyclosporine, minocycline, oritavancin and ritonavir against Rift valley fever virus. Thus, the spectrum of antiviral activities of existing antiviral agents could be expanded towards other viral diseases.
  • Rembeck, Karolina; Maglio, Cristina; Lagging, Martin; Christensen, Peer Brehm; Färkkilä, Martti Antero; Langeland, Nina; Buhl, Mads Rauning; Pedersen, Court; Morch, Kristine; Norkrans, Gunnar; Hellstrand, Kristoffer; Lindh, Magnus; Pirazzi, Carlo; Burza, Maria Antonella; Romeo, Stefano; Westin, Johan; NORDynamIC Grp (2012)