Origin and Mutations of Hong Kong New H5 Influenza Viruses

1997年，H5N1型禽流感病毒在香港传播给人类。虽然由于血凝素对furin和PC6蛋白酶的敏感性，该病毒可引起全身感染，在鸡中具有高致死率，但它们在小鼠中的毒力显示出两组不同的病毒：1组，50%小鼠（MLD_<50>）的致死剂量在0.3 ~ 11 PFU之间，2组，MLD_<50>大于10^3 PFU。在我们的模型中，一些H5N1病毒未能产生全身性感染表明，多种因素导致哺乳动物中H5N1感染的严重程度。此外，我们通过鸡对水禽分离物进行的实验表明，在自然界中维持在野生水禽中的无毒病毒在鸡中传播时具有成为高致病性的潜力。本研究中分离的一系列毒力突变体不仅有助于深入了解毒力获得的机制，而且还可能提供一种有用的工具，与反向遗传学相结合，从质粒中产生流感病毒。

An H5N1 avian influenza A virus was transmitted to humans in Hong Kong in 1997. Although the virus causes systemic infection and is highly lethal in chickens because of the susceptibility of the hemagglutinin to furin and PC6 proteases, their virulence in mice revealed two distinct groups of viruses : group 1, for which the dose lethal for 50 % of mice (MLD_<50>) was between 0.3 and 11 PFU, and group 2, for which the MLD_<50> was more than 10^3 PFU. The failure of some H5N1 viruses to produce systemic infection in our model indicates that multiple, factors contribute to the severity of H5N1 infection in mammals. In addition, our experimental passages of a waterfowl isolate through chickens demonstrated that avirulent viruses maintained in wild waterfowl in nature have the potential to become highly pathogenic while circulating in chickens. The series of virulence mutants isolated in the present study not only lend insight into mechanisms of virulence acquisition but may also provide a useful tool, in combination with reverse genetics, with which to generate influenza viruses from plasmids.