Speaker
Description
The interferon-induced and antivirally active human GTPase MxA represents a major interspecies-barrier for influenza A viruses (IAVs) of avian origin that has to be overcome in order to establish a new lineage in the human population. As a consequence, all human-adapted IAVs, including the pandemic 1918 and the pH1N1 virus as well as all their descendants, encode adaptive mutations in their nucleoproteins allowing MxA escape. In contrast, avian IAVs lack such amino acids. Intriguingly, bat Mx1 from Carollia perspicillata and Sturnira lilium (both hosts of bat IAV) was previously shown to be antivirally active against avian IAV with comparable efficiency as the human counterpart MxA. To evaluate whether bat IAV are thus resistant to human MxA, we infected cells stably expressing either functionally active MxA or the antivirally inactive MxA mutant MxAT103A with bat chimeric viruses, designated SC35M-H17N10 and PR8-H18N11. These viruses encode the internal proteins of either H17N10 or H18N11 plus surface glycoproteins of classical H7N7 or H1N1, respectively. Interestingly, viral growth of both chimeric viruses was completely abrogated in MxA expressing cells but not in the MxAT103A expressing control cell line. Consistently, while PR8-H18N11 was highly pathogenic in mice lacking a functional Mx protein, MxA transgenic mice were resistant to infection. These surprising findings suggests that the adaption process of bat IAV to bat Mx proteins did not result in MxA resistance, which is why bat IAV are like avian IAV highly sensitive to human MxA.
| Choose primary session | Evolution and Emerging viruses |
|---|---|
| Choose secondary Session | Innate Immunity |
