NS1 is the fluid for "flu-transmission".

The development of modern medicine has allowed us to conquer numerous infectious diseases; however, we human beings constantly face threats from novel infectious diseases that have been previously unrecognized. These so-called “emerging infectious diseases” are often caused by zoonotic pathogens, which mostly originate in wild animals (1, 2). Human diseases, such as AIDS, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), Ebola viral disease, and pandemic influenza are all caused by such pathogens. To cause zoonosis, the pathogens that originate in animals must cross the species barrier and transmit to humans. If these pathogens are able to efficiently transmit from human to human, a pandemic would result, endangering the lives of humans globally. Aquatic wild birds harbor a large gene pool of influenza A viruses that have been the source of influenza pandemics. Although influenza A viruses can infect a wide range of species, host restriction usually constrains their interspecies transmission; however, some mammalian-adaptive mutations have been identified in hemagglutinin (HA) and Polymerase Basic 2 (PB2) that allow avian influenza viruses to overcome the species barrier and become transmissible via the airborne route among ferrets (3). In addition, PB1 has been shown to confer to airborne transmission to H5N1 viruses (4). For over 25 y, Webster’s group has conducted surveillance of avian viruses at Delaware Bay, New Jersey, and has investigated the biological properties of the isolated H1N1 avian viruses in mammalian models (5, 6). Surprisingly, some of the H1N1 avian isolates transmitted via the airborne route in a ferret model without prior adaptation (5–7), suggesting no adaptive mutations were required for these viruses to become transmissible. By comparing the genomes of the transmissible and nontransmissible viruses, Zanin et al. (7) identify differences in the PB2, PB1, PB1-F2, PA-X, NS1, and NEP genes that are potentially associated with airborne transmissibility. A lossof-function study revealed the potential role of an amino acid substitution at position 213 of the NS1 protein in the airborne transmission, although this substitution alone was not sufficient for airborne transmissibility (Fig. 1). The findings of Zanin et al. that avian H1N1 viruses isolated from wild birds can be airbornetransmissible in mammals without prior adaptation raises an alarm over the pandemic potential of avian H1N1 viruses circulating in wild birds in North America, and highlights the importance of continuous surveillance of avian viruses to monitor genetic markers of transmissibility. Understanding of the molecular mechanisms of pathogenicity and transmissibility of avian viruses is important for preventing future pandemics by proactively mitigating risk through identification and control of pandemic potential-bearing influenza viruses in nonhuman animals. When the extent of virus replication in the upper respiratory tracts of mammals is low, transmission Avian H1N1 influenza viruses NS1