Recorded During the Keystone Symposia Conference on:
Framing the Response to Emerging Virus Infections (S2), Oct 14-18, 2018 | HKU, Hong Kong
This Keystone Symposia Virtual Access was made possible by a grant from the Croucher Foundation and The University of Hong Kong.
Influenza virus is an ever-evolving human pathogen that presents a constant threat to global public and animal health. Therefore, there is an undeniable need to identify the missing links – both host and viral – that are important for influenza virus pathogenesis to develop alternative, effective and long-lasting anti-influenza strategies. We have discovered that human histone deacetylases, HDAC1 and HDAC2 possess anti-influenza properties and are a component of host innate response against influenza. We found that RNA interference-mediated knockdown of HDAC1 and 2 expression augmented the influenza A virus (IAV) growth in A549 cells by more than 3- and 4-fold, respectively. Further, both HDAC1 and 2 exert their anti-IAV function via viperin, an interferon-stimulated gene known to inhibit IAV infection. We found that the expression of viperin was reduced by 58% and 53% in HDAC1- and 2-depleted cells, respectively, in response to IAV infection. However, like other antiviral host factors, influenza antagonizes HDAC1 and 2, and by using the same pathway, to undermine their antiviral function. We found that IAV downregulates the level of HDAC1 and 2, primarily at polypeptide level in A549 cells that can be recovered to almost 100% level in the presence of a proteasome inhibitor. The HDAC1 and 2 are prototypic members of class I HDACs and are closely related in structure and function. Hence, in many heterologous conditions, HDAC1 and 2 behave practically like “twins”. The data generated so far indicate that, in IAV-infected cells, HDAC1 and 2 also behave in a similar fashion. Interestingly, IAV also antagonizes them both in a similar manner. Nevertheless, future investigations will reveal further similarities and differences in anti-influenza viral mechanisms of host HDAC1 and 2.
Recorded During the Keystone Symposia Conference on:
Framing the Response to Emerging Virus Infections (S2), Oct 14-18, 2018 | HKU, Hong Kong
This Keystone Symposia Virtual Access was made possible by a grant from the Croucher Foundation and The University of Hong Kong.
The limited protection of current commercial vaccines necessitates the investigation of novel vaccine strategies for unpredictable outbreaks. To investigate the feasibility of using vaccines derived from Group 1 influenza A virus to induce broadly cross-reactive immune responses against multiple influenza subtypes, we tested a panel of sequential 4-dose immunization regimens in mice. Mice were treated with inactivated (seasonal H1N1, pandemic H1N1 and H5N1) and vaccinia virus-based H5N1 live-attenuated vaccines in different combinations.
Mice were then challenged by viruses of either Group 1 (H1N1) or Group 2 (H3N2, H7N7) influenza virus. All studied sequential 4-dose vaccinations could induce some degrees of heterosubtypic protection in mice. Amongst all these regimens, the combined use of inactivated and live-attenuated vaccines could achieve the best heterologous protection. These results highlight the synergistic effect of combining different vaccine platforms to enhance heterosubtypic protection against influenza viruses.
Recorded During the Keystone Symposia Conference on:
Framing the Response to Emerging Virus Infections (S2), Oct 14-18, 2018 | HKU, Hong Kong
This Keystone Symposia Virtual Access was made possible by a grant from the Croucher Foundation and The University of Hong Kong.
Recorded During the Keystone Symposia Conference on:
Framing the Response to Emerging Virus Infections (S2), Oct 14-18, 2018 | HKU, Hong Kong
This Keystone Symposia Virtual Access was made possible by a grant from the Croucher Foundation and The University of Hong Kong.