H5N1 Avian Virus - Case Study Example

Running Head: H5N1 AVAIN VIRUS H5N1 Avian virus of the of the of the Avian Influenza or Bird Flu, as it commonly referred to, is an infection which is caused by the H5N1 virus. The natural hosts of this virus are wild birds, in particular water fowls, who carry these viruses in their intestines while themselves remaining asymptomatic. Recently, H5N1 virus is not only leading to an increasing number of epizootics, but has also been implicated in several epidemics in humans. The Avian influenza virus is unique in several aspects. It has a unique structure of the HA structural protein which not only confers host specificity to the virus but is also implicated in enhancing the virulence of the organism. Moreover, this virus also has the ability to undergo antigenic drifts and antigenic shifts. The emergence of new strains of Avian influenza virus is of major public health concern because of the impending threat of a pandemic that it poses. Currently, the virus does not possess the ability of being transmitted amongst humans and it has been postulated that one this quality is acquired it would lead to potentially devastating consequences in the form of a pandemic. Till date, no vaccine for the prevention of H5N1 infection amongst humans exists. Moreover, the treatment options for infection are also limited viz. oseltamivir and zanamivir. Therefore, further research needs to be undertaken in order to develop new vaccines against these organisms and better medications to combat the infection if once contracted. Moreover, vigilant surveillance of outbreaks and epidemics of bird flu is also imperative. Arqam [Course] Running Head: H5N1 AVAIN VIRUS 23rd April 2009 H5N1 Avian virus Avian Influenza or Bird Flu, as it commonly referred to, is an infection which is caused by the H5N1 virus. The natural hosts of this virus are wild birds, in particular water fowls, who carry these viruses in their intestines while themselves remaining asymptomatic (Auewaraku 404). The transmission of this virus to domesticated birds such as ducks, chickens and turkeys, can lead to outbreaks and epidemics of infection amongst these birds, causing a large number of them to be killed (Centers for Disease Control and Prevention). Recently, H5N1 virus is not only leading to an increasing number of epizootics, but has also been implicated in several epidemics in humans. The mode of transmission of this virus has been described as being feco-oral amongst birds, whereas humans contract the disease via contact with airborne particles from infected poultry or while contact with the poultry or their fecal matter e.g. during food preparation (Fleming 1066). The first human infection with H5N1 was witnessed in 1997 in Hong Kong, as a result of which six out of the eighteen people affected died. Eversince, several similar outbreaks of human infection have been observed in various regions of the world and this has become an important public health concern (Auewaraku 404). At present, there are two different clades of the H5N1 which have been identified to be circulating amongst poultry. Amongst these, three subgroups from the clade 2 have been shown to infect humans viz. subclades 2.1, 2.2, and 2.3 Centers for Disease Control and Prevention). Infections in humans appear on a spectrum, ranging in variety and severity from relatively milder infections such as conjunctivitis to potentially serious ones such as pneumonia and can even lead to death (Centers for Disease Control and Prevention). The increasing outbreaks of human infection with H5N1 are of prime concern as this organism is highly pathogenic. It has a unique ability to infect humans and this poses a threat to the human race as this virus might have the potential to evolve into a form which is transmissible from person to person (Auewaraku 404). In the past, the world has witnessed several outbreaks of influenza, causing significant morbidity and mortality. If a new strain of this virulent organism emerges, it can lead to potentially catastrophic outbreaks of influenza in biologically naïve human hosts, claiming thousands of human lives. Thereby, it is important to study in detail the structure and molecular and cellular mechanisms of disease and evolution of H5N1 virus, as this would help in planning strategies aimed at keeping a check on the further spread of this organism and in the development of preventive measures such as vaccines to combat any further epidemics of this disease. Influenza A viruses – Molecular structure and its role in pathogenesis The H5N1 is a strain of influenza, belonging to the subgroup of Influenza A viruses. The influenza A viruses are unique from other viruses in that they are classified on the basis of the two main surface glycoproteins viz. hemagglutinin (HA) and neuraminidase (NA). Till date, 16 different HA subtypes and 9 different NA subtypes have been identified. This constitutes a genetic reservoir which is amenable to reassortment and thus can lead to the emergence of potentially highly virulent strain (Subbarao 393). Since several different combinations of these two glycoproteins are possible, numerous different strains of Influenza A virus exist. Almost all the subtypes of Influenza A have been shown to infect birds. However, only three known A subtypes of influenza viruses viz. H1N1, H1N2, and H3N2 have been shown to affect humans currently (Centers for Disease Control and Prevention). Generally, the Influenza A viruses have a low potential to infect humans and till date, no reported cases of human to human transmission of Avian Influenza viruses have been reported. There was, however, a seroprevalence ranging from 1 to 38% for H4 through H13 subtypes of Influenza A viruses reported amongst poultry workers in China. In the same population, the seroprevalence for H5 viruses was found to be around 7 % (Subbarao 393). The HA protein is of vital importance for the Avian Influenza viruses since this protein determines the host range of these viruses. By the virtue of the specificity for receptor recognition and binding, the HA protein determines the capacity to inhabit a wide range of host tissues. Studies have shown that the H5 HA is specific for the avian receptor which contains sialic acid (SA) which is linked to galactose molecule via a α2, 3 linkage. The human receptor differs from the avian receptor in that it contains an α 2, 6 linked SA. Thereby, in order to cause human to human transmission a switch from the avian receptor type to the human receptor site is required (Chen et. al.). Moreover, the HA gene is also important in determining the virulence and thus the disease severity in poultry (Subbarao 395). Till date, all the human influenza virus HA genes identified have been shown to possess an Arg residue located at the cleavage site between the HA1 and HA2 domains (Subbarao 395). Another feature of the HA gene found in the H5 influenza virus which is revealed on nucleotide sequence analysis, is the presence of multiple basic amino acids in the intervening region of the cleavage site located between the domains H1 and H2. This is a particular feature found in the highly virulent strains (discussed below) of Avian Influenza viruses (Subbarao 395). The significance of the presence of these basic amino acids in this region is that they allow the cleavage of the HA gene into HA1 and HA2 but proteases other than the specific trypsin-like protease originally required for this cleavage (Subbarao 395). This property is of vital importance to the virus in that it allows these viruses to spread systematically. By such means the virus gains access to tissues other than the normally inhabited tissues (e.g. respiratory and alimentary tract) and cause infection in novel sites such as the brain, heart and blood vessels (Subbarao 395). Keeping in view the acquisition of the capability to achieve cleavage of the HA gene via proteases other than the trypsin-like proteases, it has been postulated that if the virus via the process of evolution, acquires a ubiquitously cleavable HA, it would lead to serious consequences since the virus would then attain a very high degree of virulence and would become lethal (Subbarao 396). Moreover, the highly virulent strains also demonstrate the presence of the Arg-Lys-Lys-Arg motif. Several other features which have been shown to confer high virulence status to the Influenza A virus include the presence of a four amino acid sequence insertion viz. Arg-Gln-Arg-Arg, next to the cleavage site and the presence of glycosylation sites (Subbarao 393). Low Pathogenic versus Highly Pathogenic Avian Influenza A Viruses On the basis of the molecular structure of the viruses, their virulence and the pathogenesis, the Avian Influenza A viruses have been categorized into highly pathogenic (HPAI) and low pathogenic (LPAI) subtypes. These subtypes differ in the severity of the disease caused. Thereby, the LPAI cause mild disease in the poultry while HPAI have been shown to cause severe disease in poultry and can even result in significant mortality. Moreover, both these subtypes have the tendency to cause disease in humans. Analysis of samples from human subjects inflicted by this disease during the different outbreaks reported has shown that the subtypes H5 and H7 can infect humans and result in HPAI. The infection caused by these HPAI can vary in severity from mild infections, caused by H7N3 and H7N7, to severe and potentially life threatening infection, caused by H5N1 and H7N7. Data collected by the CDC has shown that since 2003, an aggregate of about 400 infections in humans have occurred via highly pathogenic strains of the Avian Influenza virus (H5N1). These infections have been scattered throughout several regions of the world including different countries in Asia, Africa, the Pacific, Europe and the Near East (Centers for Disease Control and Prevention). Certain LPAI have also been implicated in causing infections in humans and these include H7N7, H9N2, and H7N2. These subtypes cause mild infections such as conjunctivitis, upper respiratory tract infections (URTI), etc (Centers for Disease Control and Prevention). Antigenic Drift and Antigenic Shift Influenza viruses are a unique group of viruses that have a capacity to frequently undergo changes and genetic reassortment thereby leading to the evolution of new strains with novel properties. Influenza viruses attain this evolution via two main process viz. antigenic drift and antigenic shift. Influenza A viruses have the ability to undergo both these changes and thus are in a constant dynamic state of evolution and pose a challenge to the humans (Centers for Disease Control and Prevention). Antigenic Drift refers to the small changes in the genetic makeup of viruses which occurs as a result of genetic mutations. This is a relatively common phenomenon and leads to the production of viral strains which do not significantly differ from the parent strain. The phenomenon of antigenic drift occurs most commonly in the region of the gene encoding for structural proteins such as hemagglutinin and neuraminidase. Antigenic drift leads to minor antigenic variations in the virus which are not recognized by the human immune system and thus, humans despite having immunity against the parent strain are susceptible to infection by the newly evolved strains. This is of particular importance in the development of vaccines against influenza viruses and in the planning and execution of prevention strategies (Centers for Disease Control and Prevention). On the other hand, Antigenic Shift is a phenomenon whereby genetic reassortment takes place. The influenza virus genome has a segmented structure. This facilitates in the exchange of gene segments between two different strains of viruses which coincidentally happen to be infecting the same cell. Such an exchange can occur if dual infection occurs in a host with both the human and avian strains of the influenza virus (Chen et. al.). The threat of an H5N1 pandemic Research has shown that there are three main prerequisites for a pandemic. These include the emergence of a novel subtype of a virus to which the human subjects are biologically naïve and its introduction in the human race, the infection that follows should then manifest itself in the host and should be severe in nature and lastly, the virus should be transmissible from person-to-person in order to maintain the chain of transmission. The growing concern nowadays is that the only requirement that the Avian Influenza virus lacks is the capability of transmission from human to human. If via evolution, the virus acquires this ability, a catastrophic pandemic of a highly virulent strain of the influenza virus would result. Thereby, it is of prime importance to harness the spread of this virus at this stage and vigilantly monitor its spread in order to avoid potentially hazardous consequences in the future. In conclusion, the H5N1 virus belongs is a strain of Influenza A viruses. It is usually found in the intestines of wild birds and can cause infections in domesticated birds. This infection can range in severity from mild to severe and in recent decades, an increasing incidence of highly pathogenic strains causing severe and sometimes lethal infections in poultry have been found. The Avian influenza virus is unique in several aspects. It has a unique structure of the HA structural protein which not only confers host specificity to the virus but is also implicated in enhancing the virulence of the organism. Moreover, this virus also has the ability to undergo antigenic drifts whereby, minute changes in the genetic makeup of the organism occur leading to outbreaks and epidemics of infections in individuals who are not immune to the newly acquired genetic makeup of the virus. This has implications in the development of vaccines and in the execution of prevention strategies. Another unique feature of the organism is the capability to undergo antigenic shifts – a phenomenon whereby exchange of genetic material occurs between different strains of the virus co-infecting a cell and leads to genetic reassortment. The emergence of new strains of Avian influenza virus is of major public health concern because of the impending threat of a pandemic that it poses. Currently, the virus does not possess the ability of being transmitted amongst humans and it has been postulated that one this quality is acquired it would lead to potentially devastating consequences in the form of a pandemic. Till date, no vaccine for the prevention of H5N1 infection amongst humans exists. Moreover, the treatment options for infection are also limited since the viral strains identified in the past epidemics have been shown to be resistant to typical anti viral agents such as amantadine and rimantadine. The only drugs found to be effective against these viruses are oseltamivir and zanamivir (Centers for Disease Control and Prevention). Therefore, further research needs to be undertaken in order to develop new vaccines against these organisms and better medications to combat the infection if once contracted. Moreover, vigilant surveillance of outbreaks and epidemics of bird flu is also imperative to keep a check on the further spread of the organism and the emergence of other new potentially lethal strains. Figure 1: Alignment and comparison of complete HA coding sequence for the A/Hong Kong/156/97 virus isolate. Adapted from Subbarao (1998) Figure 2: Phylogenetic relationship of the HA1 domain of the hemagglutinin gene of representative avian H5 viruses and the H5 virus isolated from a human. Adapted from Subbarao (1998) References Auewarakul, Prasert, et al. "Codon volatility of hemagglutinin genes of H5N1 avian influenza viruses from different clades." Virus Genes (2009): 404-407. Chen, Li-Mei, et al. "Genetic Compatibility and Virulence of Reassortants Derived from Contemporary Avian H5N1 and Human H3N2 Influenza A Viruses." PLoS Pathogens (2008): 4(5): e1000072. Prevention, Centers for Disease Control and. "Avian Influenza: Current Situation." (2007): 1-4. Subbarao, Kanta. "Characterization of an Avian Influenza A (H5N1) Virus Isolated from a Child with a Fatal Respiratory Illness." Science (1998): 393-396. Read More