Introduction
Avian influenza also is known as bird flu and results from viruses acclimatized to some birds. People may be infected with avian influenza when they get into contact with the infected birds or infected fluids from the birds (Capua and Dennis 10). In this report, the discussion is about the evolution of avian influenza, characteristics of the virus, epidemiology of the virus, as well as the mode of transmission. Moreover, the paper talks about the gene expression of the virus, infection of the human by the virus, evolution of avian influenza's vaccines, and criticisms surrounding evolution of the virus.
Overall features of the avian flu virus
Influenza viruses are habitually found in casings with an up to eight-fold segmented portion of single strand RNA genome with a negative polarity. Specific viruses that cause avian influenza are part of the Orthomyxoviridae family and belong to the genus Influenza virus A (Klenk, Matrosovich, and Stech 14). Influenza genera are three – A, B, and C; the only the viruses of influenza A do infect the birds. To diagnose, one has to isolate and characterize the virus since infectivity in birds may result in numerous clinical signs. These may, in turn, vary depending on the strain of the virus, the host, environmental conditions, immune status of the host, as well as existence of any exacerbating organisms (Peiris et al. 243).
The neuraminidase (N or NA) and the haemagglutinin (H or HA) transmembrane glycoproteins form the basis of antigenic determinants of influenza viruses A and B (Klenk, Matrosovich, and Stech 13). They are capable of educing immune and subtype-specific reactions that are sufficiently defending within and only partially defensive across various subtypes. Influenza A viruses have 16 H (H1 - H16) and 9 N (N1 - N9) subtypes when grouped regarding the antigenicity of the glycoproteins (Klenk, Matrosovich, and Stech 8). The various groups are often validated when analyzing the nucleotide phylogenetically and deducing the amino acid series of HA and NA genetic materials respectively.
Pathogenesis of avian influenza virus
Influenza diseases exist in nature among birds. Undomesticated birds globally bear the virus in their intestines but do not make them sick. Nevertheless, avian flu is infectious among the birds hence can make domestic birds such as ducks, chickens, and turkeys to be ill (Rose 33). The sick birds can pass the virus through nasal discharges, saliva, and feces. Predisposed birds may contract the virus when they are exposed to the infected secretions, the surfaces contaminated with the infected secretions or excretions from infected birds. The risk of acquiring the virus is diminished for most people since the virus does not usually infect humans. However, human infections by some subtypes of avian influenza have been noted since 1997 (Klenk, Matrosovich, and Stech 4). Rarely has it been reported that the influenza viruses are spread from one ill person to another hence its transmission has been limited and inefficient. The disorder is majorly found in countries where families raise the birds for their meals. These birds, in turn, contaminate the living areas as they roam about and are slaughtered for meals.
H5N1 is a highly pathogenic virus that has progressed through complex genetic alterations from the progenitor strain of 1996 (Abdelwhab and Hafez 648). It consists of no less than 10 groups of genetically and antigenetically different strains, which have passed on the disease to the wild birds and domestic poultry in several countries. H5N1 virus often binds to the receptors on distal alveolar and bronchiolar cells (macrophages and type II pneumocytes) giving SA-α-2,3-Gal (Rose 34). The receptors have also been noticed in tracheal tissue, pharynx, nasal, intestinal, neuronal, hepatic, splenic, epithelial, renal, and T cells, as well as neonatal respiratory tissues. The viral replication of H5N1 has been exhibited in ex vivo nasopharyngeal, tonsillar tissue cultures and adenoid exclusive of evident SA-α-2,3-Gal receptors an indication that receptor specificity is complex (Gupte 9).
Infections in humans
Even though the bird flu viruses do not often infect people, few cases of human contagion due to the virus have been noted (Gupte 13). The sick birds always spread the virus shedding their saliva, feces, and mucus. Avian influenza viruses can infect humans when enough viruses get into an individual's eyes, mouth, or nose. The virus may be in space as droplets or dust that a person may breathe in or on a contaminated surface, which one may touch and, in turn, use the same hands to touch the eyes, mouth, or nose. People may contract the virus when they make unprotected contact with the infected birds or contaminated surfaces. Nonetheless, some infectivity has been discovered where no contacts made directly were witnessed to have taken place (Capua and Dennis 10). Illnesses in humans always range from docile to severe with regards to the stage of the disease.
Epidemiology of avian influenza virus
Domestic poultry’s direct cause of infection can hardly be verified, but the outbreaks often begin by making contacts with the water birds. Several strains that are in circulation among the wild birds are either mildly pathogenic or non-pathogenic for capon. However, there are cases where virulent strain emerges because of gene mutation as was witnessed in the eastern part of the United States of America between 1983 and 1987 (Capua and Dennis 11). Swine is crucial in turkeys’ infection with the swine flu virus whenever they are close. Some mammals seem not to be engrossed in the epidemiology of HPAI. The H5 avian flu virus human infection of 1997 in Hong Kong has led to a reassessment of the role that avian groups play in the epidemiology of human disease (Capua and Dennis 12).
Once the avian flu virus seeps into the household poultry, it is vastly communicable; hence, undomesticated birds are no longer a necessity in its spread (Gupte 9). The infected birds do excrete bugs in high concentration in their feces, as well as ocular and nasal discharges. Movement of the infected birds then enhances its spread in the flock through direct contact but can as well be erratic. Transmission can be through the air when the birds are close. Infection readily takes place in birds through the installation of the virus into the trachea or conjuctival sac (Klenk, Matrosovich, and Stech 6). Research shows that the virus can be recovered at the height of the disease from the albumen and yolk of eggs. Possibilities of vertical spread remain uncertain, and it is unlikely that the infected embryos can endure and hatch. Hatching of eggs among the infected flock would indeed be associated with a substantial risk.
Mode of transmission/infection of avian influenza virus
Transmission of the flu takes place readily among the birds. The virus is contained in the saliva, feces, and nasal secretions shed by birds (Gupte 7). Those not infected can easily contract the virus when they get into contact with the secreted matter carrying the virus. The mild form of the flu at times goes undetected as the infected birds have ruffled feathers and lay fewer eggs. However, there is a pathogenic form of the flu, which spreads faster. It affects the internal organs of the birds, and its mortality rate is almost 100 percent with the sick birds dying within 48 hours (Gupte 8).
At first, it was believed that H5N1 could not infect humans, but this has been proven otherwise through advanced medical research (Gupte 8). Avian flu A viruses can be conveyed to humans from animals by an intermediate host like a pig or when people get into contact with surfaces contaminated with the virus. Influenza A virus possesses eight varying gene segments. The segmentation allows the creation of a new species of virus especially when different species attack the same animal or person (Klenk, Matrosovich, and Stech 4). Changing of the genetic makeup of the virus may enable the virus to be more infectious, and this is referred to as "antigenic shift.” It can easily result into an influenza pandemic as people will not be immune to the new virus.
Increased cases of infection among humans by the viruses often involve getting in touch with the infected poultry especially dying or ill chickens. Some potential modes of transmission among the infected patients include conjuctival and direct intranasal inoculation during swimming in unhygienic water (Gupte 8). Other means include hand contamination as well as self-inoculation into the upper respiratory region or the eye. Improved adaptation of the avian flu viruses in human hordes can significantly change the transmission paths and increase the chances of person-to-person spread.
Clinical features of molecular aspects of Avian Influenza virus replication
Clinical features vary significantly and are swayed by numerous factors including the species affected, age, the virulence of the infection, sex, contemporaneous diseases, and the environment (Capua and Dennis 14). In the case of extremely pathogenic avian infection, the disorder may appear in a flock and can kill numerous birds either with minimal signs of ruffled feathers, depression, and fever or without premonitory symptoms. Other birds show a staggering gait and signs of weakness. Hens often lay soft-cased eggs at first but soon bring to an end laying of eggs. Sick birds mostly stand or assemble in a semi-comatose condition with their heads making contact with the ground. Wattles and combs are oedematous and cyanotic, and at times have ecchymotic or petechial hemorrhages at their tips. The birds are always excessively thirsty, and profuse watery diarrhea is frequently present while the victims may toil for respiration. Hemorrhages may come about on areas of the skin without feathers and death rate can vary from 50 to 100% (Klenk, Matrosovich, and Stech 11).
The signs of the disease in broilers include severe inappetence, depression, and increased mortality. Oedema of the neck or visage and neurological symbols such as ataxia and torticollis may be observed. The ailment in the turkeys resemble that observed in layers, however; it lasts about 2 or 3 days more and is intermittently going together with swollen sinuses (Klenk, Matrosovich, and Stech 13). Domesticated geese and ducks show indications of diarrhea, depression, and inappetence that are comparable to those in layers. Younger birds can exhibit neurological signs.
Gene expression
The life cycle of the influenza virus can be classified into the following stages: entering the host cell, vRNPs' entry into the nucleus; viral genome transcription and replication; exporting the vRNPs from the nucleus; assembling and budding at the host cell plasma membrane.
Transcription of Avian Influenza virus during the infection cycle
Virus replication and transcription
Replication and transcription of IAV genomic RNAs often take place in the nucleus being catalyzed by the complex trimeric viral polymerase made up of subunits like PA, PB1, and PB2. Replication of the viral RNA starts with the generation of a positive intellect copy of the vRNA, also known as the complementary RNA. Transcription of the viral RNA begins after PB2 binds to the 5′-cap configuration of the host mRNAs. PA’s endonuclease activity goes ahead to snatch the cap structure together with the 10-13 nucleotides, which are contained in the cap serve in the mRNA viral synthesis as a primer (Peiris et al. 243). Viral mRNA synthesis is accomplished by the polymerase bustle of PB1. Reviewing of the nuclear removal of viral mRNAs takes place in Fodor and York. Transcription then continues until the complex polymerase stops close to the last part of the viral RNA at polyadenylation.
Translation
The translation machinery within the host cell translates viral mRNAs of influenza. Therefore, numerous translation factors like eIF4G (eukaryotic initiation factor-4G), eIF4A and eIF4E often interact with the polymerase complexes of the viral mRNAs (Klenk, Matrosovich, and Stech 19). After IAV infection, the synthesis of protein of the host cell, which is a limited and preferential translation of IAV mRNAs takes place. Specifically, the lately created nuclear mRNAs can be depleted of their cap formations through "cap-snatching" hence ensuing in speedy breakdown before nuclear export takes place and conversion.
Intracellular trafficking
At the start of the disease, RNPs discharged from the infectious flu virus are taken into the nucleus from the cytosol. All the component proteins of RNP have at least a single NLS (nuclear localization signal) essential for nuclear import (Gupte 13). Even though all constituent proteins of RNP contain their NLSs, NP contributes significantly to the importation of RNP. Influenza A virus assemblage takes place at the membrane of the host cell hence the lately synthesized RNPs has to be taken out of the nucleus (Peiris et al. 252). Therefore, have to move in the reverse direction in comparison to their parental RNPs. Some other two influenza proteins, NEP, and M1 are required for RNP export. M1’s C-terminal domain interacts with RNP while M1-fastening to the RNP aids in masking the NLSs to the RNP. In the meantime, M1 directly interacts with NEP, a viral protein that has an NES signal. Membrane buildup of the virus often sets off MAPK (mitogen-activated protein kinase) cascade activation hence inducing RNP export. It represents an auto-regulative system, which synchronizes the time of RNP export with the virus burgeoning (Klenk, Matrosovich, and Stech 17).
Human Infection with Avian Influenza Virus
More often than not, influenza viruses do mutate quickly. Such mutations do occur spontaneously within a virus or if more influenza strains exchange their genetic materials when they become close. Different mutations of influenza viruses occur. These include antigenic shifts. In such a mutation, large segments of RNA interchange between distinct influenza virus. Another type of mutation is antigenic drifts. In this case, small sequences of RNA are changed. New strains are created by antigenic shifts. For instance, a pandemic of swine flu, in 2009, was as a result of a virus, which had genetic component from avian influenza, pig influenza, as well as strains of human influenza (Allegra 3).
The genome of influenza virus has extraordinary plasticity due to a high rate of mutation as well as its differentiation into eight distinct molecules of RNA. Such segmentation or differentiation permits recurrent genetic exchange via reassortment of the segment within hosts that are infected by two distinct influenza viruses. A strain of disease-causing avian influenza virus (AIV), in 2011, mutated in such a manner, rendering ineffective the existing vaccine against the new strain of avian flu. In some occasions, a flu virus can mutate in a manner, which can make it infect a novel species. Some pandemic of influenza takes place when a novel strain of this virus emerges, which is pathogenic to people or human. The 1918 case represents the worst fatal pandemic in the current history of influenza. It spread fast and claimed many people in the globe in numbers of millions.
Evolution of Avian Influenza Virus’ Vaccines
The initial vaccine produced (live-attenuated) for the virus was done in the year 1933.
In the year 1996, the first or initial AIV (H5N1) detection was done within Guangdong Province in ill geese. After the detection, scientist started coming up with vaccines against AIV pandemic. A scientist named Hilleman jump-begun production of vaccine by sending to manufacturers, virus sample and encouraging them to come up with a vaccine against AIV within four months. Following such request, an inactivated vaccine against H5N2 was created out of a low disease-causing virus and was employed in 2004 during the outbreak of H5N2 within China as a buffer or protection zone vaccination (Klenk, Matrosovich, and Stech 27).
A concerted effort to release or make a vaccine for a novel strain (H1N1) in U.S, started following the identification of the virus by the scientists. In the process of manufacturing, the virus grew slowly that dependent on the virus being cultivated within chicken eggs (Compans, and Orenstein 154). Recently, scientists released vaccine called Newcastle vectored live virus, which exhibits a significant promise for prevention of high disease-causing influenza within the field as well as Newcastle disease among chickens. Approximately more than thirty billion vaccines’ doses have been utilized in China as well as other nations in controlling H5N1 AIV.
Viral mutations do trigger recommendations for the influenza vaccine compositions. They are influenced by the continuous surveillance identifying the various strains of the virus circulating in humans (Hannoun 1092). The vaccine strains should be identified based on the emergence of new viral strains. The choice is made depending on the best estimation of the possibility of the predominant strain. Avian virus H5N1 circulated in the domestic and wild fowl in the years 2003 as well as 2007 while spreading in humans (Hannoun 1093). It triggered the development of human vaccines that were not fully utilized due to the low contagiousness as well as low risks of the circulating forms to humans. Further, the 2009 H1N1 viral epidemic led to the development of monovalent pandemic vaccines for use in various parts of the world.
The annual vaccine strain updating system enhances the preparedness to tackle new viral strains that may emerge. The efficacy of the influenza vaccines is affected by the mismatch of the strains. Additionally, the viral drift from the targeted strain into new forms reduces the vaccine efficiency due to specificity in the immune response. The decisions on the vaccine strains depend on the assessment of epidemiologic data, pathogenic potential, antigenic strain identification, as well as the transmissibility. The genetic and antigenic characterization of the virus contributes to the identification of suitable vaccine viruses (Swayne 823).
Criticism as well as Controversies concerning the evolution of AIV
Some nations have employed trade restrictions or ban about importing birds as well as their products. For example, restriction on semen or eggs from Asian states, which are experiencing cases of H5N1 virus. For instance, China prohibits the importation of poultry from Japan, Thailand, S. Korea, or Vietnam (Harris, Sulston, and Coggon 179). Such restrictions do have an influence on SPS agreement or treaty of WTO (Harris, Sulston, and Coggon 180). WTO member countries in line with SPS agreement, are alerting the SPS Committee concerning trade restrictions imposed to exporting poultry from the affected nations (Harris, Sulston, and Coggon 180). Currently, these nations have justification for trade restrictions based on animal health as well as the highly disease-causing characteristic of the H5N1 virus within a population of birds, which implies that such trade limitations cannot be questioned under the agreement of SPS requirements that there must be a scientific reason for restricting trade on health ground. Nonetheless, the contribution of trade within the unprecedented regional spread avian influenza virus is currently not fathomed.
There are human rights issues concerning the outbreak of avian influenza virus about government compensation on the destruction of individual property. In the global declaration about human rights, ideally right to property is acknowledged (Harris, Sulston, and Coggon 179). Such a right, is never absolute as a government can violate it for many reasons, for example, in the protecting the health of the public. Compensation for individual property destroyed by the state in the interest of the public can be one of the strategies of obeying right to property (Harris, Sulston, and Coggon 179). FAO, WHO, as well as OIE, have emphasized the significance of compensation to halt the outbreak of H5N1. However, there is a debate on the issue.
There is controversy about the principles of government role as well as an accusation on cover-ups within some countries. For example, there is accusation on the governments of Indonesia as well as Thai for trying to cover-up outbreaks of H5N1 within their regions (Tulchinsky and Varavikova 181). Similar accusations were made against China for trying to cover-up the outbreak of SARS. It is unclear or implicit that cover-up of diseases can constitute an infringement of existing principles or laws of state role. For that reason, controversy on the reactions of the governments of Indonesia or Thai to the outbreaks of diseases, there are concerns about leaving to states or governments to decide on the course of action.
The concept of seasonal flu shots is not fully welcome by most of the citizens in the affected countries. The controversy lingers between whether the flu shots are necessary. It is recommended that all the people from six months old (infants) to adults are expected to be given a shot of flu vaccine every year (Cameron 297). There are divisions among the expert opinions on the requirements. Ideally, the doctors, academics, and researchers question the scientific basis for the influenza vaccine. They argue that the influenza virus does not cause the majority of the flu-like illnesses and may not accrue the full benefits of widespread vaccination. Another argument is that the vulnerable groups like the elderly are not fully protected by the influenza vaccine. Worse is that some consider or believe the influenza vaccine is a mere placebo that confers psychological effect rather than the ideal protection. Conversely, the proponents of the vaccine claim that it can establish herd immunity among the population (Tulchinsky and Varavikova 181).
In summary, the many routes of entry of AIV, especially H5N1, shows that protection from the infection with the virus can be achieved through adequate hand hygiene, protection of eyes, as well as respiratory tract. Research on avian influenza should continue to develop effective vaccines to stop future outbreaks. Ideally, a case of the virus in one place is a global health threat everywhere, for that reason; global cooperation must be fostered instead on leaving it to the responsibility of governments where a case or outbreak occurs.
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