Article Alert: Avian Influenza Virus NS2 Protein Facilitates Viral Adaptation to Mammals

Species-specific host restriction barriers curtail the ability of avian influenza viruses (AIV) to productively infect mammalian hosts. The human host factor acidic nuclear phosphoprotein 32A/B (huANP32A/B), which is essential for human-adapted influenza A virus (IAV) replication, is nevertheless pivotal in constraining AIV polymerase (vPol) activity and therefore limits cross-species pathogenicity. HuANP32A/B lacks a 33-residue insert that includes a SUMO-interacting motif (SIM)-like sequence that is crucial for AIV vPol function. Human infection is thus possible only with the acquisition of additional mutations. However, various highly pathogenic AIVs (such as H5N1 and H7N9) are able to infect humans without these adaptations. How this occurs was unclear.

In their new study, Sun et al. present exciting insight into how these highly lethal AIVs infect humans (1). The researchers found that the AIV NS2 protein acts as a co-factor to break through host restriction by facilitating avian viral ribonucleoprotein (vRNP) assembly and promoting mammalian ANP32A/B-avian vRNP interactions. The key feature in NS2, a conserved C-terminal SIM that mediates noncovalent interactions with SUMO1/2/3-conjugated proteins, was shown to be requisite for NS2’s enhancement of the avian-signature polymerase activity. The findings by Sun et al. suggest a mechanism for early infection by AIV of a mammalian host that allows nonadapted vPol to establish productive replication so that it can gain additional advantageous mutations. Thus, this work identifies an important step in the AIV mammalian host adaptation process.

GeneTex maintains a constantly expanding viral infectious disease reagent catalog, which includes the widely cited Influenza A virus PB2 protein antibody (GTX125926) used in this study (1). For more details, please see the highlighted products below and visit www.genetex.com.