tetano
Editor, Senior Moderator
J Virol. 2016 Feb 17. pii: JVI.03172-15. [Epub ahead of print]
[h=1]The C-terminal Tail of TRIM56 Dictates Antiviral Restriction of Influenza A and B Viruses by Impeding Viral RNA Synthesis.[/h] Liu B[SUP]1[/SUP], Li NL[SUP]1[/SUP], Shen Y[SUP]1[/SUP], Bao X[SUP]2[/SUP], Fabrizio T[SUP]3[/SUP], Elbahesh H[SUP]1[/SUP], Webby RJ[SUP]3[/SUP], Li K[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Accumulating data suggest that tripartite motif-containing (TRIM) proteins participate in host responses to viral infections, either by acting as direct antiviral restriction factors or through regulating innate immune signaling of the host. Of >70 TRIMs, TRIM56 is a restriction factor of several positive-strand RNA viruses, including three members of the family Flaviviridae (yellow fever virus, dengue virus and bovine viral diarrhea virus) and a human coronavirus (OC43), and this ability invariably depends upon the E3 ligase activity of TRIM56. However, the impact of TRIM56 on negative-strand RNA viruses remains unclear. Herein, we show TRIM56 puts a check on replication of influenza A and B viruses in cell culture, but does not inhibit Sendai virus or human metapneumovirus, two paramyxoviruses. Interestingly, the anti-influenza activity was independent of the E3 ligase activity, B-box, or coiled-coil domains. Rather, deletion of a 63-residue long, C-terminal tail portion of TRIM56 abrogated the antiviral function. Moreover, expression of this short C-terminal segment curtailed the replication of influenza viruses as effectively as that of full-length TRIM56. Mechanistically, TRIM56 was found to specifically impede intracellular influenza virus RNA synthesis. Together, these data reveal a novel antiviral activity of TRIM56 against influenza A and B viruses and provide insights into the mechanism by which TRIM56 restricts these medically important orthomyxoviruses.
[h=4]IMPORTANCE:[/h] Options to treat influenza are limited and drug-resistant influenza virus strains can emerge through minor genetic changes. Understanding novel virus-host interactions that alter influenza virus fitness may reveal new targets/approaches for therapeutic interventions. We show here that TRIM56, a tripartite-motif protein, is an intrinsic host restriction factor of influenza A and B viruses. Unlike the case with its antiviral actions against positive-strand RNA viruses, the anti-influenza activity of TRIM56 was independent of the E3 ligase activity. Rather, expression of a short segment within the very C-terminal tail of TRIM56 inhibited the replication of influenza viruses as effectively as that of full-length TRIM56, by specifically targeting viral RNA synthesis. These data reveal the remarkable multifaceted activity of TRIM56 which has developed multiple domains to inhibit multiple viral families. They also raise the possibility of developing a broad-spectrum, TRIM56-based antiviral approach for addition to influenza prophylaxis and/or control strategies.
Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
PMID: 26889027 [PubMed - as supplied by publisher]
[h=1]The C-terminal Tail of TRIM56 Dictates Antiviral Restriction of Influenza A and B Viruses by Impeding Viral RNA Synthesis.[/h] Liu B[SUP]1[/SUP], Li NL[SUP]1[/SUP], Shen Y[SUP]1[/SUP], Bao X[SUP]2[/SUP], Fabrizio T[SUP]3[/SUP], Elbahesh H[SUP]1[/SUP], Webby RJ[SUP]3[/SUP], Li K[SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Accumulating data suggest that tripartite motif-containing (TRIM) proteins participate in host responses to viral infections, either by acting as direct antiviral restriction factors or through regulating innate immune signaling of the host. Of >70 TRIMs, TRIM56 is a restriction factor of several positive-strand RNA viruses, including three members of the family Flaviviridae (yellow fever virus, dengue virus and bovine viral diarrhea virus) and a human coronavirus (OC43), and this ability invariably depends upon the E3 ligase activity of TRIM56. However, the impact of TRIM56 on negative-strand RNA viruses remains unclear. Herein, we show TRIM56 puts a check on replication of influenza A and B viruses in cell culture, but does not inhibit Sendai virus or human metapneumovirus, two paramyxoviruses. Interestingly, the anti-influenza activity was independent of the E3 ligase activity, B-box, or coiled-coil domains. Rather, deletion of a 63-residue long, C-terminal tail portion of TRIM56 abrogated the antiviral function. Moreover, expression of this short C-terminal segment curtailed the replication of influenza viruses as effectively as that of full-length TRIM56. Mechanistically, TRIM56 was found to specifically impede intracellular influenza virus RNA synthesis. Together, these data reveal a novel antiviral activity of TRIM56 against influenza A and B viruses and provide insights into the mechanism by which TRIM56 restricts these medically important orthomyxoviruses.
[h=4]IMPORTANCE:[/h] Options to treat influenza are limited and drug-resistant influenza virus strains can emerge through minor genetic changes. Understanding novel virus-host interactions that alter influenza virus fitness may reveal new targets/approaches for therapeutic interventions. We show here that TRIM56, a tripartite-motif protein, is an intrinsic host restriction factor of influenza A and B viruses. Unlike the case with its antiviral actions against positive-strand RNA viruses, the anti-influenza activity of TRIM56 was independent of the E3 ligase activity. Rather, expression of a short segment within the very C-terminal tail of TRIM56 inhibited the replication of influenza viruses as effectively as that of full-length TRIM56, by specifically targeting viral RNA synthesis. These data reveal the remarkable multifaceted activity of TRIM56 which has developed multiple domains to inhibit multiple viral families. They also raise the possibility of developing a broad-spectrum, TRIM56-based antiviral approach for addition to influenza prophylaxis and/or control strategies.
Copyright ? 2016, American Society for Microbiology. All Rights Reserved.
PMID: 26889027 [PubMed - as supplied by publisher]