流感病毒研究工具

Influenza Virus Research

Influenza (flu) is a respiratory infection in mammals and birds. It is caused by an RNA virus in the family Orthomyxoviridae. The virus is divided into three main types (Influenza A, Influenza B, and Influenza C), which are distinguished by differences in two major internal proteins (hemagglutinin (HA) and neuraminidase (NA)). Influenza virus type A is found in a wide variety of bird and mammal species and can undergo major shifts in immunological properties. Influenza virus type B is largely confined to humans and is an important cause of morbidity. Little is known about Influenza virus type C, which is not an important source of morbidity.

Influenza A is further divided into subtypes based on differences in the membrane proteins hemagglutinin (HA) and neuraminidase (NA), which are the most important targets for the immune system. The notation HhNn is used to refer to the subtype comprising the hth discovered Hemagglutinin (HA) protein and the nth discovered neuraminidase (NA) protein. The influenza viral Hemagglutinin (HA) protein is a homo trimer with a receptor binding pocket on the globular head of each monomer, and the influenza viral neuraminidase (NA) protein is a tetramer with an enzyme active site on the head of each monomer. Subtypes are further divided into strains; each genetically distinct virus isolate is usually considered to be a separate strain.

Influenza viruses that are known to infect human include the following sub-types. H1N1 virus that caused "Spanish Flu" (A/BrevigMission/1/1918(H1N1)) and seasonal flu (A/Brisbane/59/2007(H1N1), A/New Caledonia/20/1999(H1N1), and A/Solomon Islands/3/2006 (H1N1)) and a reassorted virus (A/California/04/2009(H1N1)) that caused the 2009 swine flu outbreak; H2N2 virus that caused the "Asian Flu"; H3N2 virus that caused the "Hong Kong Flu"; H5N1 "The Bird Flu" virus (A/Anhui/1/2005 (H5N1), A/Vietnam/1203/2004, A/Vietnam/1194/2004 (H5N1), A/bar-headed goose/Qinghai/14/2008 (H5N1), A/turkey/1/2005 (H5N1), A/Indonesia/5/2005 (H5N1)) that was the world's major influenza pandemic threat until the Swine Flu Pandemic of 2009; H7N7 virus that has unusual zoonotic potential; H1N2 is currently endemic in humans and pigs; and H9N2, H7N2, H7N3, H10N7 viruses.

Influenza research involves investigating molecular virology, pathogenesis, host immune responses, genomics, and epidemiology regarding influenza. The main goal of influenza research is to develop influenza countermeasures such as vaccines, therapies and diagnostic tools. Influenza virus vaccination is an effective approach to control influenza virus infection and pandemic spread of the virus. Each seasonal influenza vaccine contains hemagglutinin (HA) and neuraminidase antigen from three influenza subtype viruses-one subtype Influenza A H3N2 virus, one regular seasonal Influenza A H1N1 virus (not the 2009 H1N1 virus), and one Influenza B virus. Because of the influenza virus continues to mutate (antigen minor drifting or antigen major shifting) over time, the viruses in the vaccine change each year based on international surveillance and scientists' estimations about which types and strains of viruses will circulate in a given year. About 2 weeks after vaccination of the influenza viral antigen, antibodies that provide protection against influenza virus infection develop in the body.

Protection mechanism of influenza vaccine is well established to be neutralizing antibody (polyclonal human antibody) raised against influenza viral protein antigen such as the hemagglutinin (HA ) and neuraminidase (NA) protein antigen. Neutralizing antibody can block virus binding to host cells, block viral entry into host cells, and kill infected host cells. Recombinant monoclonal antibody (Mab, mouse monoclonal antibody, rabbit monoclonal antibody, chimeric monoclonal antibody, humanized monoclonal antibody) raised against the hemagglutinin (HA ) antigen or cloned from human B-cells (human monoclonal antibody) have shown to be promising anti-influenza infection product candidates.

At present, there are only three licensed anti-Influenza drugs namely Relenza (Zanamivir - ZMV), Tamiflu (Oseltamivir - OTV) and Amantadine/Rimantadine. The latter targets the M2 ion channel whereas the other compounds target neuraminidase (NA) and were designed through structure-based enzyme inhibitor programmes. Neuraminidase promotes influenza virus release from infected cells and facilitates virus spread within the respiratory tract. The neuraminidase inhibitors interfere with the release of progeny influenza virus from infected host cells, thereby halts the spread of infection in the respiratory tract. The influenza neuraminidase inhibitors are associated with very little toxicity and are far less likely to promote the development of drug-resistant influenza. In addition, the neuraminidase inhibitors are effective against all neuraminidase subtypes and, therefore, against all strains of influenza, a key point in epidemic and pandemic preparedness. Because of a broader antiviral spectrum, better tolerance, and less potential for emergence of resistance than is seen with the M2 inhibitors, the neuraminidase inhibitors represent an important advance in the treatment of influenza.