Transmission of influenza A/H5N1 viruses in mammals.

Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans and cause severe respiratory disease and fatalities. Currently, these viruses are not efficiently transmitted from person to person, although limited human-to-human transmission may have occurred. Nevertheless, further adaptation of avian H5N1 influenza A viruses to humans and/or reassortment with human influenza A viruses may result in aerosol transmissible viruses with pandemic potential. Although the full range of factors that modulate the transmission and replication of influenza A viruses in humans are not yet known, we are beginning to understand some of the molecular changes that may allow H5N1 influenza A viruses to transmit via aerosols or respiratory droplets among mammals. A better understanding of the biological basis and genetic determinants that confer transmissibility to H5N1 influenza A viruses in mammals is important to enhance our pandemic preparedness.

Predicting 'airborne' influenza viruses: (trans-) mission impossible?

Repeated transmission of animal influenza viruses to humans has prompted investigation of the viral, host, and environmental factors responsible for transmission via aerosols or respiratory droplets. How do we determine-out of thousands of influenza virus isolates collected in animal surveillance studies each year-which viruses have the potential to become 'airborne', and hence pose a pandemic threat? Here, using knowledge from pandemic, zoonotic and epidemic viruses, we postulate that the minimal requirements for efficient transmission of an animal influenza virus between humans are: efficient virus attachment to (upper) respiratory tissues, replication to high titers in these tissues, and release and aerosolization of single virus particles. Investigating 'airborne' transmission of influenza viruses is key to understand-and predict-influenza pandemics.

Genesis of pandemic influenza.

During the last decade the number of reported outbreaks caused by highly pathogenic avian influenza (HPAI) in domestic poultry has drastically increased. At the same time, low pathogenic avian influenza (LPAI) strains, such as H9N2 in many parts of the Middle East and Asia and H6N2 in live bird markets in California, have become endemic. Each AI outbreak brings the concomitant possibility of poultry-to-human transmission. Indeed, human illness and death have resulted from such occasional transmissions with highly pathogenic avian H7N7 and H5N1 viruses while avian H9N2 viruses have been isolated from individuals with mild influenza. The transmission of avian influenza directly from poultry to humans has brought a sense of urgency in terms of understanding the mechanisms that lead to interspecies transmission of influenza. Domestic poultry species have been previously overlooked as potential intermediate hosts in the generation of influenza viruses with the capacity to infect humans. In this review, we will discuss molecular and epidemiological aspects that have led to the recurrent emergence of avian influenza strains with pandemic potential, with a particular emphasis on the current Asian H5N1 viruses.

Adaptation of influenza A/Mallard/Potsdam/178-4/83 H2N2 virus in Japanese quail leads to infection and transmission in chickens.

To assess the potential of quail as an intermediate host of avian influenza, we tested the influenza A/Mallard/ Potsdam/178-4/83 (H2N2) virus to determine whether through adaptation a mallard strain can replicate and transmit in quail, as well as other terrestrial birds. After five serial passages of lung homogenate a virus arose that replicated and transmitted directly to contact cage mates. To test whether adaptation in quail led to interspecies transmission, white leghorn chickens were infected with the wild-type (mall/178) and quail-adapted (qa-mall/178) viruses. The results show that mall/178 H2N2 does not establish an infection in chickens nor does it transmit, while qa-mall/178 H2N2 infects and transmits to contact chickens causing clinical signs like depression and diarrhea. Completed sequences indicate six amino acid changes spanning four genes, PB2, PB1, HA, and NP, suggesting that the internal genes play a role in host adaptation. Further adaptation of qa-mall/178 in white leghorn chickens created a virus that replicated more efficiently in the upper and lower respiratory tract. Sequence analysis of the chicken-adapted virus points to a deletion in the neuraminidase stalk region.