Expression of importin-α isoforms in human nasal mucosa: implication for adaptation of avian influenza A viruses to human host

Abstract

BackgroundTransportation into the host cell nucleus is crucial for replication and transcription of influenza virus. The classical nuclear import is regulated by specific cellular factor, importin-α. Seven isoforms of importin-α have been identified in human. The preference of importin-α3 of avian influenza virus and -α7 isoform of human strains during replication in human cells was previously identified. In addition, both avian and human influenza viruses were shown to use importin-α1 isoform for their replication.FindingThe mRNA levels of importin-α1, −α3, and –α7 isoforms in human respiratory tract was determined by real-time RT-PCR. The results indicate that mRNA level of importin-α7 was significantly higher than that of importin-α1 (p-value < 0.0001) and importin-α3 (p-value < 0.0001) isoforms in human nasal mucosa while importin-α1 was detected as the highest expression importin-α isoform in lung tissues.ConclusionsThese results may explain the preference of importin-α7 isoforms in seasonal influenza viruses in human upper respiratory tract and may suggest a selective pressure toward importin-α7 in human respiratory tract infection of an avian virus.

Differential Behaviours and Preferential Bindings of Influenza Nucleoproteins on Importins-α

“…The A/NP TAIL was isolated from a human strain of influenza A virus and interacted preferentially with importin-α7. This is consistent with the importins-α expression pattern in the human respiratory track [52] as well as of previously reported work [31]. It is of note that PB2 isolated from human strains also preferentially bind to importin-α7, while avian PB2s tend to interact with importin-α3 [28].…”

Immune responses in influenza A virus and human coronavirus infections: an ongoing battle between the virus and host

“…With the increasing accumulation of knowledge of molecular interactions between host cells and viruses, additional host molecules and normal biological processes [ 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66• , 67 , 68 , 69 ] were found to participate in the viral replication cycle (summarized in Table 2 ). To clarify the roles of these molecules and processes in virus infection, host genetic determinant screening [ 70 , 71 , 72 ], immunomics and Public Health Omics [ 73 ], host lipid omics [ 74 •• ] and characterization of the epigenetic landscape [ 75 ] were used to supplement conventional analyses.…”

“… [ 52 ] Preferential usage of importin-alpha7 isoforms by seasonal IAV in the human upper respiratory tract makes it a target of selective pressure. [ 64 ] Vesicular trafficking IAV IAV infection modulates vesicular trafficking and induces Golgi complex disruption. [ 68 ] IAV enhances its propagation through modulating Annexin-A1 dependent endosomal trafficking.…”

“…The crucial role of the IFN response makes it a preferred target for viral evasion. Besides NS1, multiple virus-encoded molecules including the nucleoprotein [ 64 ], the fusion peptide of HA2 (HA2-FP), HA1 and some variants of polymerase subunits PB1-F2, PB1, PB2, PA all counteract the interferon response [ 91 ]. Interestingly, some host cellular molecules are also utilized by IAV to block IFN expression.…”

Avian Influenza Virus Tropism in Humans

“…According to Gabriel et al, AIV prefer on utilizing importin α3 (in avian host), whereas adapted human AIV prefer on utilizing both importin α3 and importin α7 (in human host) to start transport of viral proteins into nucleus [134]. The fact that importin α7 is more widely distributed in the upper and lower respiratory tracts of humans than importin α3 suggests that the adapted human AIV may be under selective pressure to prefer importin 7 [137]. Hence, a retain preference to importin α3 and an additional preference towards importin α7 is needed by AIV to allow efficient nuclear import in human cells [134,137,138].…”