Avian Influenza Virus: Mechanism, Epidemiology And Control

Early 2009, eight cases of human H5N1 infections is very pathogenic avian influenza (HPAI) virus, with 5 cases of death, were reported in China. This again makes the sign of the possible pandemic in the world, may be caused by avian-origin influenza virus. More H5N1 is in the spotlight in the world, not only for scientists but also for ordinary people. How much we know about this virus. Where the virus will go and where they come from? We can avoid the possibility of pandemic influenza. Human will conquer this agent is effective? Of course, we can from our list of questions to find out answers.

Influenza virus, as a pathogenic entity for the chickens, has been known since 19th century. But in 1997, the first cases of human infection with the death and identified as the H5N1 virus strain found in Hong Kong SAR (Special Administrative Region), China, reminds us of virus-host is extending its reach from birds to mammalians. In 2003, when the outbreak of SARS (Severe acute respiratory syndrome), a fatal human case is diagnosed with a surprising isolation of H5N1 virus. This is the first human infection case in mainland China. Now we know many countries (15 countries to early 2009) there is the human H5N1 influenza virus infection. These countries have been the epicenters of the influenza virus, including in addition to seasonal influenza virus H5N1. In 2005, even natural reservoir host, move the birds found infected with the epidemic more than 6,000 dead birds that are involved. Therefore, the special in this topic, we invite scientists from Hong Kong and mainland China recently to review progress in the H5N1-related research field with seven reviews and one script in the original study endocytosis and H5N1 influenza virus. Website for the Bird Flu Information consisting of avian influenza information from the various aspects are also introduced. This is not only a database and a platform for researchers Knowledgebase but also for the community.

First we invited two prominent scientists, Yuelong SHU and Paul CHAN, from China CDC and the Chinese University of Hong Kong respectively to overview the situation of human infection of H5N1 in mainland China and the experience in Hong Kong. They summarize the frontline epidemiological, clinical and virological characteristics of human avian influenza virus infections based on the national surveillance system in mainland China and give a chronological and archival description of the events in Hong Kong. These accounts would greatly be appreciated for the future preparedness of possible pandemics. From the current human reported H5N1 virus infection cases, most of the patients could trace back with contacts of birds (chicken or ducks) though there were some reports with evidence of limited human-to-human transmission. Therefore domestic or wild bird infection control is the key for the H5N1 human infection. Hualan CHEN from Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, discusses the situation of animal infection and its control in China.

As we know, more and more species, especially some mammalian species such as cats and tigers, are becoming victims or carriers of H5N1, the expansion of the host range and interspecies transmission of H5N1 virus is worrying. The mechanism underlying this change is elusive and scientists are working together to tackle this problem from our understanding of the virus itself and the host factors affecting this change. George F. GAO, Frank LIU and colleagues from CAS Key Laboratory of Pathogenic Microbiology and Immunology review our current knowledge of the interspecies transmission and host factors involved: from virus receptor usage to host proteins interacting with the virus or virus components.

Basic research always gives us some tantalizing hope for the control of virus infection. Nucleoprotein (NP) is an important structural protein of influenza virus, being the key component of the ribonucleoprotein complex. The structure of NP is revisited by Andy NG, Jia-Huai WANG and Pang-Chui SHAW from Dana-Farber Cancer Institute and the Chinese University of Hong Kong. Correlations are made between the sequence conservation and the atomic structure. This provides the basis for identifying structurally and functionally important regions for inhibitor design. Crystal structures of some parts of the polymerase complex, PA alone or PA with part of PB1, have been solved. Zihe RAO, Yingfang LIU and colleagues from Institute of Biophysics, CAS, Tsinghua University and Nankai University, provide an overview of the structure and potential target for the new drug design. For a long time the drug target for influenza viruses was basically limited to two proteins, hemagglutinin (HA) and neuraminidase (NA). Hopefully, the basic findings on nucleoprotein and polymerase will lead to some new drug leads.

Clinically the human cases of H5N1 infection manifest some ARDS (acute respiratory distress syndrome) symptoms, similar to SARS infection. Therefore unraveling the molecular pathogenesis mechanism will help save life. Chengyu JIANG, from Peking Union Medical College, Chinese Academy of Medical Sciences, who has long been involved in the study of molecular pathogenesis of SARS, describes our current understanding of the molecular pathogenesis of H5N1 in human infection and presents their recent work on the clathrin-dependent endocytosis of H5N1 influenza virus.

H5N1 virus research is a scientifically fascinating field and a much-needed field for life-saving. In the future we ought to know why and how H5N1 virus expands its host range. Compared to SARS, H5N1 is more complicated. Is there any chance human beings will be in a position to conquer this devastating virus? The understanding of H5N1 virus also helps us to combat other influenza viruses, such as the swine flu that has recently surfaced from Mexico. Though readers would see we have made some progress in the field, this tantalizing record is far from our ultimate goal of control of this virus. Molecular pathogenesis, virus evolution, human immune response and vaccine development, drug discovery and other basic research must be addressed.