ABSTRACT
Influenza A viruses (IAVs) take advantage of the host acetylation system for their own benefit. Whether the nucleoprotein (NP) of IAVs undergoes acetylation and the interaction between the NP and the class I histone deacetylases (HDACs) were largely unknown. Here, we showed that the NP protein of IAV interacted with HDAC1, which downregulated the acetylation level of NP. Using mass spectrometry, we identified lysine 103 as an acetylation site of the NP. Compared with wild-type protein, two K103 NP mutants, K103A and K103R, enhanced replication efficiency of the recombinant viruses in vitro. We further demonstrated that HDAC1 facilitated viral replication via two paths: promoting the nuclear retention of NP and inhibiting TBK1-IRF3 pathway. Our results lead to a new mechanism for regulating NP acetylation, indicating that HDAC1 may be a possible target for antiviral drugs.
ABSTRACT
New strategies in vaccine development are urgently needed to combat emerging influenza viruses and to reduce the risk of pandemic disease surfacing. Being conserved, the M2e protein, is a potential candidate for universal vaccine development against influenza A viruses. Mycobacterium tuberculosis Hsp70 (mHsp70) is known to cultivate the function of immunogenic antigenpresenting cells, stimulate a strong cytotoxic T lymphocyte (CTL) response, and stop the induction of tolerance. Thus, in this study, a recombinant protein from the extracellular domain of influenza A virus matrix protein 2 (M2e), was fused to the C-terminus of Mycobacterium tuberculosis Hsp70 (Hsp70c), to generate a vaccine candidate. Humoral immune responses, IFN-γ-producing lymphocyte, and strong CTL activity were all induced to confirm the immunogenicity of M2e.Hsp70c (Hsp70(359-610)). And challenge tests showed protection against H1N1 and H9N2 strains in vaccinated groups. Finally these results demonstrates M2e.Hsp70c fusion protein can be a candidate for a universal influenza A vaccine.
