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Table of Contents   
REVIEW ARTICLE  
Year : 2010  |  Volume : 21  |  Issue : 4  |  Page : 586-590
Mongrelised genetics of H1N1 virus: A bird's eyeview


Department of Pedodontics and Preventive Dentistry, RajaRajeswari Dental College & Hospital, Mysore Road, Kumbalgodu, Bangalore, Karnataka, India

Click here for correspondence address and email

Date of Submission25-Dec-2009
Date of Decision25-Mar-2010
Date of Acceptance02-Sep-2010
Date of Web Publication24-Dec-2010
 

   Abstract 

H1N1 influenza, also known as "novel H1N1 virus" has led to a "global outcry." This virus is more virulent when compared with other seasonal flu viruses. Virulence may change as the adaptive mutation gene increases within the virus. A study at the US Centre for Disease Control and Prevention published in May 2009 found that children had no preexisting immunity to the new strain as they showed no cross-reactive antibody reaction when compared with adults aged 18-64 years, who showed a cross-reactive antibody reaction of 6-9% and older adults with 33% immunity. This review article depicts H1N1 virus, its virulence with genetic evolution potential and preventive protocol for the dental professionals. This would allow us to comprehend the changes in the disease process and contribute in its prevention as "prevention is better than cure."

Keywords: H1N1 virus, immunity, mongrelised genetics

How to cite this article:
Nagarathna C, Shakuntala B S, Navin H K, Maru VP. Mongrelised genetics of H1N1 virus: A bird's eyeview. Indian J Dent Res 2010;21:586-90

How to cite this URL:
Nagarathna C, Shakuntala B S, Navin H K, Maru VP. Mongrelised genetics of H1N1 virus: A bird's eyeview. Indian J Dent Res [serial online] 2010 [cited 2019 Oct 17];21:586-90. Available from: http://www.ijdr.in/text.asp?2010/21/4/586/74235
With the new H1N1 virus continuing to cause illness, hospitalizations and deaths the world over, it is wise for us to stay informed about its genetic evolution, which made it highly virulent, and practice standard precautions to protect ourselves and our patients as this pandemic evolves.

H1N1 infection is a respiratory disease of type A influenza virus that causes regular outbreaks in pigs (swine). It is a new subtype of the "A" strain, known since 1918,. [1] Every virus has eight genes and the strains of flu virus jump from one species to another without any genetics or with reassortment of the eight genes (antigenic shift). [2]


   Genetic Evolution Top


The following description explains how the influenza A (H1N1) virus genetically evolved from 1918 to 2009 with respect to virulence [Figure 1].
Figure 1: Genetic evolution of H1N1 virus from 1918 to 2009

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  • 1918 Spanish influenza - simultaneous appearance in humans and swine. In the spring of 1918, the first wave of the virus emerged in humans, beginning in the United States and sweeping through Canada, Europe and Asia. It is thought that in the summer the virus mutated or reasserted with avian influenza virus, whose origin is still unknown, creating an even more virulent strain of the virus. As a result, a violent wave of disease swept through the world in the fall. At the same time, a virus was infecting swine, causing a disease strikingly similar to the disease seen in humans infected with influenza A H1N1. After the pandemic disappeared in humans, the viral disease was seen in swine seasonally for many decades.

    A veterinarian named Dr. Richard Shope was the first to isolate any influenza virus. He isolated swine influenza A H1N1 virus in 1931. He discovered experimentally that swine influenza A H1N1 virus of 1931 could be transmitted from sick pigs to healthy animals. He also reported that the swine influenza virus and the human influenza virus of 1918 were the same or at least very closely related. He also showed that the swine influenza A H1N1 virus of 1918 had changed very little in the swine population.
  • 1957 Spanish influenza - Although the influenza A virus of 1918 continued to circulate in pigs unchanged, the human influenza A H1N1 virus underwent antigenic shift quickly. After 1918, the human H1N1 serotypes drifted until they were no longer related to that of the swine strain. Different serotypes of human H1N1 continued to seasonally circulate until 1957 when the virus reasserted with another strain, producing influenza A H2N2, giving rise to the second pandemic.
  • 1968 Hong Kong influenza - Similarly, the influenza A H2N2 virus again reasserted with another strain to produce influenza H3N2, giving rise to the third pandemic in Hong Kong.

    The swine influenza virus was isolated from humans in 1974, confirming that it was zoonotic. In 1976, an outbreak of respiratory disease occurred at an army base in Fort Dix, New Jersey. A swine-origin influenza A H1N1 was isolated and determined to be the cause of this outbreak.

    Coincidentally, H1N1 virus reemerged in the human population in 1977, probably as a result of accidental laboratory release, and continues to circulate through the population. The H1N1 strains alternated with the H3N2 strain. The H3N2 human influenza virus was introduced into the swine population in the 1990s. The H1N1 and H3N2 virus reasserted. The mutated virus contained the hemagglutinin [H] and neuraminidase [N] antigens of H1N1 virus and several proteins of H3N2. This triple-reasserted influenza A HIN1 was isolated from 17-year olds frequently exposed to swine with severe respiratory disease in 1998. Between 1999 and 2009, 11 cases of triple-reasserted swine-origin H1N1 infections were reported.
  • 2009 swine flu outbreak - In April 2009, a new swine-origin influenza A H1N1 virus causing severe respiratory disease was isolated in California. This virus was found to be quadruple-reasserted H1N1. The triple-reasserted H1N1 virus reasserted with Eurasian-like swine H1N1 producing the quadruple H1N1 influenza A virus, which is currently in circulation. [3] The Centres for Disease Control and Prevention (CDC, US) determined that the present strain contained genes from four different flu viruses - North America swine influenza, North American avian influenza, human influenza and swine influenza virus typically found in Asia and Europe - "an unusual mongrelised mix of genetics sequences." [4],[5],[6],[7],[8],[9],[10],[11]

    On 22 nd May 2009, the WHO chief Dr. Margaret Chan said that the virus must be closely monitored as it could combine with ordinary seasonal influenza and change in unpredictable ways. [12] However, an article published in the Times of India, dated 3 rd September 2009 (Bangalore, edition), reported a study conducted by American scientists who allowed three different flu viruses to compete against the H1N1 virus inside ferrets. They found that H1N1 virus was far more infectious and prevailed inside the body while other viruses faced stiff resistance, which made them conclude that there are less chances of H1N1 virus mixing with other seasonal flu viruses to form a new so-called reassortant virus.



   Nomenclature Top


In July 2009, WHO experts named this virus as "2009 pandemic H1N1 influenza virus" to distinguish it from the current seasonal H1N1 virus and, as of August 2009, the CDC began referring to it as the "novel H1N1 virus."

Some authorities objected to calling the flu outbreak "swine flu." The US Agriculture Secretary, Tom Vilsack, expressed concerns that this would lead to misconception that pork is unsafe for consumption. [13] Then, CDC began referring to it as "novel influenza A H1N1." [14] In the Netherlands, it was originally called "pig flu," but is now called "Mexican flu" by the national health institute and in the media. South Korea and Israel briefly considered calling it the "Mexican virus." [15] Later, the South Korean press used "SI," the short form for swine influenza. Taiwan suggested the names "H1N1 FLU" or "new flu," which most local media now use. [16] The World Organisation for Animals Health proposed the name "North American influenza." [17] The European Commission adopted the term "novel flu virus." [18]


   Antigenic Variation Top


Influenza viruses have long been known for their ability to change, creating new strains of virus that infect naive populations. Influenza viruses change by two processes, antigenic drift and antigenic shift.

Antigenic drift [19],[20] is the process by which influenza viruses continuously change their antigenic characteristics. This is an important process driven by the immune response to influenza viruses. Antibody targeted against the viral antigens bind and neutralize the virus-containing antigen. Influenza viral DNA polymerase is prone to mistakes and new genes are often produced, resulting in the production of new antigen. The accumulation of these changes over time leads to mutations, which produce hemagglutinin and neuraminidase that are not targeted by antibody. As a result, new serotypes of the viruses are produced. Antigenic drift causes past immunity against influenza to become incapable of fighting the disease caused by mutated viral strains.

Antigenic shift [21],[22],[23],[24],[25],[26],[27] is the formation of a new strain of viruses by the combination of at least two different strains. When a cell is simultaneously infected by two different strains of influenza virus, the genes of each strain become mixed during replication. As a result, when the viral components recombine, some of the genetic material from one strain of virus ends up in the other, producing a new strain with new genetic material.

It is quite clear that the swine acts as a "mixing vessel" for human and avian influenzas. Hemagglutinin binds with sialic acid on the receptor, allowing the virus to enter the cell. Hemagglutinin on avian influenza has shown to bind different types of sialic acid than human influenza hemagglutinin. Swine have both these types of sialic acid in their respiratory tracks. As a result, swine can be infected with either human or avian influenza, facilitating antigenic shift [28],[29] and hence the influenza virus is also called swine flu virus.


   Immunity Top


A study at the US CDC published in May 2009 found that children had no preexisting immunity to the new strain as they showed no cross-reactive antibody reaction [30] to the new strain, whereas in adults aged 18-64 years had 6-9% and older adults showed 33% immunity. [31],[32] This is one of the main reasons that led the masses from all around the globe to get infected by the current strain of virus, compelling the WHO to call it a pandemic for the first time in the last 41 years. Also, the infected individuals do develop long-term immunity; however, influenza viruses are able to overcome this immunity through antigenic drift, antigenic shift and genome reassortment. [33]


   Pathogenesis Top


The 2009 H1N1 virus is transmitted through direct contact between infected and susceptible individuals. After the virus is inhaled, it colonizes the columnar epithelial cells of the bronchial epithelium. To do this, the virus must first attach and enter into the cell, where it will replicate to form new virions, which then leave to infect other cells or individuals. [3]

Attachment and entry into the host cell

The hemagglutinin antigen binds to sialic acid residues found in glycoprotein molecules located on the host cell membrane. Hemagglutinin functions to fuse the plasma membrane together during endocytic uptake of the viral particle. To do this, however, it first requires that the hemagglutinin antigen is activated by endogenous proteases. Upon activation, bound hemagglutinin enables the virion to enter the cell. [33],[34]

Viral replication

The virus is located within a cytosolic endosome. This endosome fuses with a lysosome to form a phagolysosome. The internal pH of the phagolysosome is lower than that of the cytosolic and external environmental pH. In this acidic environment, the hemagglutinin is able to fuse the viral envelope with the plasma membrane of the phagolysosome, creating a hole through which the 2009 H1N1 RNA escapes into the cytosol. From here, the RNA travel to the nucleus. Genome replication occurs within the nucleus while viral protein synthesis and virion assembly occur within the cytosol. [33],[34] Replication occurs within 16 h of infection. [35]

Release from the cell

The 2009 H1N1 virus is an enveloped virus and thus leaves the cell by a process known as budding. [36],[37] Viral surface antigens, including hemagglutinin and neuraminidase, are inserted into the host cell membrane. This segment of the cell membrane forms a pocket containing the newly assembled virion. This pocket buds off to form the new virus. The hemagglutinin of the budded virus, however, is bound to sialic acid found on the surface of the host's cell membrane. Neuraminidase cuts the sialic acid and thereby enables the release of the virus. [33]

Host response

The 2009 H1N1 virus infection of the respiratory tract causes localized destruction of cells in the bronchial epithelium. This, in turn, induces the release of cytokines, pyrogens and other inflammatory mediators that have both a local and a systemic effect. A massive release of cytokines results in hypercytokinemia, [38],[39],[40] leading to the presentation of pathological lesions. Cell-mediated and humoral immunity also play an important role in eliminating the virus. [33]


   In vivo and in vitro Characterization of Influenza A (H1N1) Virus Top


According to Yasushi et al., most human infections with swine origin H1N1 influenza viruses (S-OIVs) seem to be mild; however, a substantial number of hospitalized individuals did not have underlying health issues, attesting to the pathogenic potential of S-OIVs. To achieve a better assessment of the risk posed by the new virus, they characterized one of the first US S-OIV isolates, A/California/04/09 (H1N1; hereafter referred to as CA 04 ) as well as several other S-OIV isolates in vivo and in vivo. In mice and ferrets, the CA 04 and other S-OIV isolates tested replicated more efficiently than a currently circulating human H1N1 virus. In addition, CA 04 replicates efficiently in nonhuman primates, causing more severe pathological lesions in the lungs of infected mice, ferrets and nonhuman primates than a currently circulating human H1N1 virus, and transmits among ferrets. In specific pathogen-free miniature pigs, CA 04 replicates without clinical symptoms. The assessment of human sera from different age groups suggest that infection with human H1N1 virus is antigentically closely related to the virus circulating in 1918, conferring a neutralizing antibody activity to CA 04 . [41]


   Preventive Protocol for the Dental Professionals Top


The dental team should screen patients for recent travel history and for symptoms of influenza, , and must segregate patients with respiratory symptoms and those who have travelled to an affected area in the last 7 days, and should consider them as suspected cases.

Patients with an acute respiratory illness should be identified at check-in and should be placed in a single-patient room with the door kept closed.

When space and chair availability permits, encourage coughing persons to sit at least 6 feet away from others in common waiting areas.

Posters for educating the patients regarding swine flu can be displayed in the dental office reception area or waiting room.

The dental team has to be prepared with proper attention to hand hygiene and coughing etiquettes. Patients and dental healthcare workers should perform hand hygiene (e.g., hand washing with antimicrobial soap and water, alcohol-based hand rub or antiseptic hand wash) after having contact with respiratory secretions and contaminated objects. [42]

The dental healthcare personnel assessing a patient with influenza-like illness should wear a fit-tested disposable N 95 respiratory as a standard precaution along with disposable gloves and gown and eye protection (e.g., goggles) to prevent direct skin and conjunctival exposure. Patients presenting a risk with respiratory symptoms or suspected of having been in contact with swine flu should be asked to wear masks.

In suspected or confirmed cases, elective dental treatment should be deferred and the patient should be advised to contact their general health care provider.

If the patient requires urgent or emergency treatment, standard precautions are to be taken and treatment is to be provided in a hospital with dental care capabilities, which provides an airborne infection isolation room (i.e., with negative-pressure air handling with 6-12 air changes per hour). Air is to be recirculated after filtration by a high-efficiency particulate air filter. [43]

For cleaning and disinfection strategies, choose a product whose label states that it is effective against "influenza A virus" and follow the label instructions for these products. [44]

Dental staff experiencing influenza-like illness should not report to work and should receive adequate treatment. [2]

 
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Correspondence Address:
Viral Pravin Maru
Department of Pedodontics and Preventive Dentistry, RajaRajeswari Dental College & Hospital, Mysore Road, Kumbalgodu, Bangalore, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-9290.74235

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