The Flu is Heading to the Zoo
The bird flu in China has raised a growing concern to medical researchers who are attempting to study the genetic behavior and sequences of the H7N9 virus together with other H7 strains and avian influenzas. Three people have been killed with approximately 10 others infected raising speculations and questions of the spread of the virus between humans to humans and birds to humans and the consequent risk of a global epidemic. Certain researchers are however worried especially since the virus has been reported to have genetic markers that will aid a faster spread within the human populations amidst claims that the virus is not yet fully adapted to humans. What is even more surprising and interesting is the observation that birds do not seem to be affected. It is therefore quite a challenge for researchers to find the source of infection. This therefore needs an understanding of the viral behavior and sequences.
Flu, also known as influenza is a highly contagious respiratory disease caused by RNA viruses of the influenza viruses’ family (Orthomyxoviridae) that mostly affects animals and birds. Some of its common symptoms include gastro-intestinal symptoms like nausea, diarrhea and vomiting, headaches, shivers, cold sweats, running noses, coughing and aching joints and limbs and fatigue (Eccles, 2005). It is mainly transmitted through the air from coughs and sneezes as well as the direct contact with birds, their nasal secretions and droppings. Viruses are essentially microscopic infectious acellular organisms with genomes that consist of nucleic acids. They are only able to replicate inside the cells of their hosts through the metabolic processes that form pools of components forming virion particles, these protect the genome and enable it to transfer to other cells (Eccles, 2005).
The difference between a virus and bacteria is very evident because a virus is not a living organism as opposed to bacteria. Viruses are not able to perform basic living functions like respiration, movement, growth and similarly do not exhibit any forms of irritability, They are however able to reproduce through their ability to replicate. Bacteria on the other hand are prokaryotic organisms with cell membranes.
The RNA viruses that cause influenza are classified into three different subgroups of Influenza virus A, B and C. The serotype H7N9 of the bird flu occurs in the group A. It has one species, the influenza A virus with a virus particle diameter size of 80 to 120 nanometers. Common hosts for it are the wild aquatic birds. When occasional transmissions to different species occur, devastating outbreaks in domestic poultry are usually caused. This often gives rise to pandemics of human influenza (Barry, 2004). Pandemics are epidemics of infectious diseases that spread through the human populations over large regions even globally resulting in high mortality rates. Of the three types of influenza the virus A is the most virulent and hence causes the most severe of diseases.
Replication and infection of influenza has multiple stages and processes. In the initial stage, influenza virus binds and enters the cells. It then delivers its genome to the site of reproduction of new RNA and viral proteins copies (Bouvier & Palese 2008). These then assemble to new particles of viruses before they exit the cell. For influenza viruses, binding is through hemagglutinin especially on epithelial cells surfaces found in the throat, nose and lungs of mammalian animals and the intestines of birds (Wagner et al., 2002). Stage two begins after the hemagglutinin has been cleaved by proteases which allow the cell to import the virus through endocytosis whereby the details of the cells are elucidated (Steinhauer 1999).
Virions often converge at the microtubule organizing center to interact with the endosomes that are acidic to finally enter the endosome they target for the release of their genomes (Liu et al., 2011). The acidity of the endosomes once inside the cells first causes part of the protein, hemagglutinin protein to fuse the vacuole’s membrane with the viral envelope and secondly the M2 ion channel allows the movement of the protons through the viral envelope. This acidifies the virus core causing it to dissemble and release the core proteins and viral RNA (Lakadamyali, 2003). The second stage is completed when these accessory proteins, viral RNA molecules and RNA-dependent RNA polymerase are released to the cytoplasm (Pinto & Lamb 2006). A complex that is then formed is transported to the cell nucleus to allow the RNA-dependent RNA polymerase to transcribe the complementary positive-sense vRNA which is either left in the nucleus or exported to the cytoplasm before translation (Cros & Palese 2003). The Golgi apparatus are usually responsible for the synthesis of new viral proteins to the surface of the cell or the transportation back to the nucleus to new viral genome particles after binding the vRNA (Kash et al., 2006). A virion is then assembled after the negative-sense vRNAs’, viral proteins and RNA-dependent RNA polymerase assembles (Nayak, Hui & Barman, 2004). The viral core proteins and the vRNA leave the nucleus and enter into a membrane protrusion created after the neuraminidase and hemagglutinin cluster to form a bulge at the cell membrane (Nayak et al., 2004). This develops to a mature virus which later on buds off with the phospholipid membrane of the host cell. After these release of the new influenza viruses, the host cell eventually dies (Drake 1993)
The influenza viruses exhibit an antigenic shift which often occurs when there are major changes in a virus’ genome. This results in assortment or recombination which then causes pandemics.
Another form this genetic change is the antigenic drift whereby the individual bases in the RNA or DNA mutates to form other bases. The point mutations are often "silent" and do not change the protein encoded by the genes. Others however have evolutionary advantages like antiretroviral resistance. When mutations occur in infected organism, disastrous effects are usually felt. Mutations occur in the absence of RNA enzymes which are used for proofreading. When this happens, the RNA-dependent RNA polymerase responsible for copying the viral genome makes an error which happens roughly after every 10 thousand nucleotides which is the approximate length of the vRNA. This results in manufacture of mutagenic influenza viruses that and hence, an antigenic drift (George, 2012). If more than one influenza virus type infects a cell, reassortment or mixing of the vRNA occurs from the separation of the genome into eight separate segments. Antigenic shifts then allow a rather quick spread of the virus by infecting the host species as well as being able to overcome their protective immunity. These mutations are responsible for the emergence and development of pandemics of the bird flu.
When a team of researchers sequenced the genomes viruses’ H7N9 and H7N7 from a variety of birds to other types of bird-flu strains, they found out that H7N9 and H7N7 were hybrids of the wild Eurasian waterfowl strains like H7N3 and H11N9. This was possible according to the scientists because the viruses were able to swap their genes in ducks before they were spread to the chickens. They are then traded with H9N2 from chickens, improving the ability of the virus to spread in chicken which is the closest poultry animal to humans. The latest strain, H7N7 has so far not infected humans (George, 2012).
Influenza researchers say that the evolutionary pathways that the viruses follow suggest that there is need for better sanitation and more surveillance particularly in poultry markets to monitor and control infections to humans. Mutational rates vary for different strains. The H7N9 virus that is limited to human-to-human for instance does not represent the initial stages of full adaptation to humans’ trajectory unlike other strains like H5N1, H3N2v and H7N7. The viral strains are however rapidly evolving exhibiting a number of complex characteristics. The H7N9 for example, constantly evolves making it more capable of infecting pigs which usually allow for the mingling of the human and bird flu viruses, making it more able to spread between humans. This evolution makes it difficult for researchers to map the source of the virus since adaptability to humans also evolves with virus evolution. The fact that symptoms of the flu in the birds are not noticeable makes it even harder for positive result in terms of management, control and prevention. Infected birds do not show symptoms probably due to their adaptability to the virus. Travel restrictions from infected countries are crucial particularly because of the high evolution rates.
Prevention of the influenza virus can be aided by drugs and vaccines. The immune response system is responsible for the prevention of viral transmission in the body. Inhibitory hormones for instance, begin by lowering the cortisol levels in the body. Influenza infected cells similarly produce huge amounts of proinflammatory hormones (George, 2012). High risk groups like pregnant women, children, people with asthma and other chronic infections are likely to succumb to influenza due to their week immunity. Anti-retroviral drugs therefore reduce the length of time which symptoms occur and prevent the virus from infecting cells through blocking the ion channel M2 protein (Monto, 2006).
References
Barry, J. M (2004). The great influenza: the epic story of the deadliest plague in history. New
York, N.Y: Viking.
Bouvier, N. M., Palese, P. The biology of influenza viruses. (2008). Vaccine. 26 Suppl 4: D49–
53.
Cros, J., Palese, P. (2003). Trafficking of viral genomic RNA into and out of the nucleus:
Influenza, Thogoto and Borna disease viruses. Virus Res 95 (1–2): 3–12.
Drake, J (1993). Rates of spontaneous mutation among RNA viruses. Proc Natl Acad Sci USA
90 (9): 4171–5.
Eccles, R (2005). Understanding the symptoms of the common cold and influenza. Lancet
Infect Dis 5 (11): 718–25.
George, Dehner. (2012). Influenza: A Century of Science and Public Health Response.
Kash, J., Goodman, A., Korth, M., Katze, M. (2006). Hijacking of the host-cell response and
Translational control during influenza virus infection. Virus Res 119 (1): 111–20.
Lakadamyali, M., Rust, M., Babcock, H., Zhuang, X. (2003). Visualizing infection of individual
Influenza viruses. Proc Natl Acad Sci USA 100 (16): 9280–5.
Liu, S. L., Zhang, Z. L., Tian, Z. Q., Zhao, H.S., Liu, H., Sun, E. Z., Xiao, G. F., Zhang, W.,
Wang, H. Z., Pang, D. W. (2011). Effectively and efficiently dissecting the infection of influenza virus by quantum dot-based single-particle tracking. ACS Nano.
Monto, A.S. (2006). Vaccines and antiviral drugs in pandemic preparedness. Emerging
Infect. Dis. 12 (1): 55–60
Nayak, D., Hui, E., Barman, S. (2004). Assembly and budding of influenza virus". Virus Res 106
(2): 147–65.
Steinhauer, D, A. (1999). Role of hem agglutinin cleavage for the pathogenicity of influenza
virus. Virology 258 (1): 1–20.
Pinto, L. H., Lamb, R. A. (2006). The M2 proton channels of influenza A and B viruses. J. Biol.
Chem. 281 (14): 8997–9000
Wagner, R., Matrosovich, M., Klenk H. (2002). Functional balance between haemagglutinin and
neuraminidase in influenza virus infections. Rev Med Virol 12 (3).
