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1、Newer respiratory virus infections: human metapneumovirus, avian infl uenza virus, and human coronaviruses Ron A. M. Fouchier, Guus F . Rimmelzwaan, Thijs Kuiken and Albert D.M.E. Osterhaus Purpose of review Recently, several previously unrecognized respiratory viral pathogens have been identifi ed
2、and several infl uenza A virus subtypes, previously known to infect poultry and wild birds, were transmitted to humans. Here we review the recent literature on these respiratory viruses. Recent fi ndings Human metapneumovirus has now been detected worldwide, causing severe respiratory tract illnesse
3、s primarily in very young, elderly and immunocompromised individuals. Animal models and reverse genetic techniques were designed for human metapneumovirus, and the fi rst vaccine candidates have been developed. Considerable genetic and antigenic diversity was observed for human metapneumovirus, but
4、the implication of this diversity for vaccine development and virus epidemiology requires further study. Two previously unrecognized human coronaviruses were discovered in 2004 in The Netherlands and Hong Kong. Their clinical impact and epidemiology are largely unknown and warrant further investigat
5、ion. Several infl uenza A virus subtypes were transmitted from birds to humans, and these viruses continue to constitute a pandemic threat. The clinical symptoms associated with these zoonotic transmissions range from mild respiratory illnesses and conjunctivitis to pneumonia and acute respiratory d
6、istress syndrome, sometimes resulting in death. More basic research into virus ecology and evolution and development of effective vaccines and antiviral strategies arerequired tolimittheimpactofinfl uenzaAvirus zoonoses and the threat of an infl uenza pandemic. Summary Previouslyunknownandemergingre
7、spiratoryvirusesarean important threat to human health. Development of virus diagnostic tests, antiviral strategies, and vaccines for each of these pathogens is crucial to limit their impact. Keywords coronavirus, infl uenza A virus, metapneumovirus, respiratory disease Curr Opin Infect Dis 18:14114
8、6.#2005 Lippincott Williams fax: +31 10 4089485; e-mail: r.fouchiererasmusmc.nl Current Opinion in Infectious Diseases 2005, 18:141146 Abbreviations HCoVhuman coronavirus hMPVhuman metapneumovirus IAV infl uenza A virus RSVrespiratory syncytial virus RTIrespiratory tract illness SARSsevere acute res
9、piratory syndrome #2005 Lippincott Williams while hMPV was detected in up to 57% of children suffering from RTIs during a single winter epidemic 10?, overall incidence estimates ran- ging from 5 to 12% are more realistic 4,6?,7?,11?,12?. In young children, the clinical symptoms associated with hMPV
10、infection are virtually indistinguishable from those caused by RSV, varying from mild upper RTI to severe pneumonia 4,5. Very severe RTI was noted in children infected with both hMPV and RSV in some studies 13,14? but not in others 6?,15?. Since hMPV and RSV infections in many studies have been show
11、n to occur in overlapping winter epidemics, co-infections with these two pathogens are not unlikely to occur, but their clinical importance requires more detailed studies. A controversy also exists with respect to the exacerbation of asthma upon hMPV infection, which was observed by some investigato
12、rs 6?,7?,1618, but not by others 19, and this remains an important question in hMPV research. Information on the prevalence of hMPV and spectrum of disease associated with infection in people of other ages and other risk groups remain anecdotal. However, hMPV infections were detected in people with
13、RTI of all ages, in the community or hospitalized, with most severe disease reported in frail elderly and immunocompro- mised individuals 4,7?,20,21. Exacerbation of chronic obstructive pulmonary disease by hMPV was reported in fi ve of 89 elderly individuals that were negative for other known patho
14、gens 22. The results of these recently published studies and those reviewed earlier 4,5 thus indicate that hMPVisan important pathogenin people of all ages. Further research is needed to obtain a better understanding of the clinical impact of hMPV infections in different populations, the full spectr
15、um of hMPV- associateddiseasesand risk factors that may beassociated with severe hMPV disease. Although signifi cant antigenic and genetic diversity has been noted for hMPV throughout the world, there is little evidence for antigenic drift over time 23?. Using animal antisera, two serotypes have bee
16、n identifi ed, each of which can be further divided into two genetic lineages 23?,24?. The full genome sequence has recently become available for each of the four genetic lineages of hMPV 25,26?,27. The relevance of the antigenic variation for the induction of protective immunity in animal models and humans is still under debate 23?, 28?,29?. It is of interest to note that reinfections with hMPV appear to occur frequently 30?, and that rein- fections reported to date were caused by genetical
