Influenza (Inf) is a major cause of morbidity and mortality worldwide. It is caused by influenza virus. The uniqueness of this virus is its ability of emergence of new strains and thereby the potential of causing pandemic.

Influenza virus belongs to the family of Orthomyxoviridae which has seven genera or types; of which three are influenza A, influenza B and influenza C and other three are Thogotovirus, Isavirus and Quaranjavirus. Influenza D has been proposed as a novel genus in the family Orthomyxoviridae.

Influenza A: Influenza A viruses are spherical or pleomorphic virus of around 100–120 nm diameter. It contains single-stranded, segmented RNA genome which is surrounded by matrix protein and envelop (Fig. 1).

Fig1. Influenza virus (schematic)

Envelop: Virus has lipid envelop that is derived from the host cell. Three surface projections are present in the envelop: Hemagglutinin (HA) and neuraminidase (NA) are two glycoproteins present with an average ratio of 4 to 1 between HA and NA and M2 protein acts as an ion channel. The length of the glycoprotein surface spikes is 10–14 nm.

Matrix protein: This layer (M1) is present under the envelop.

Viral genome consists of single stranded negative sense RNA of eight segments encoding 10 proteins: Hemagglutinin (HA), neuraminidase (NA), matrix protein 2 (M2) and matrix protein 1 (M1), non-structural proteins NS1 and NS2, and three polymerases; polymerase basic 1 (PB1), polymerase basic 2 (PB2) and polymerase acidic (PA).

Influenza B: The structure is similar to Influenza A. It has four surface proteins: HA, NA, NB and BM2.

Influenza C: It has hemagglutinin-esterase fusion (HEF) and CM2 proteins on the surface. Unlike influenza A and B, it has seven RNA segments.

Influenza A virus has been subdivided further based on HA and NA surface proteins. According to current information by Center for Disease Control and Prevention (CDC, September 2016), there are 18 HA types (H1 H18) and 11 NA types (N1–N11). Between two HA subtypes, the amino acid sequence difference is ³30%.

Viral Proteins

 Hemagglutinin (HA)

 Structure: HA is a type I glycoprotein. It is present as a rod-shaped structure with a globular head, in the form of trimmer. Each monomer of the trimmer contains the receptor binding site. The carboxyl terminal end of the protein gets anchored into the envelop and hydrophilic N terminal projects away from the virus surface.

Function: It helps in attachment of virus with the host cell receptor sialyloligosaccharide. Receptor binding site is present within the globular head. On low pH, it changes its morphology and becomes susceptible to protease. This helps in fusion process and uncoating.

It is also responsible for the hemagglutinating property of the virus, acts as the major antigenic determinant and produces neutralizing antibody.

Neuraminidase (NA) 155 It is a type II glycoprotein. Its top part is mushroom shaped, present in the form of a tetramer. It has sialidase activity and prevents aggregation of virion. Antibody against NA protects from infection.

M2 Protein

It is present on the surface of the virion and acts as H2 channel. It gets activated in the endosome by low pH and acidify the inside of the virus which helps in uncoating of virion.

Influenza Virus Genetics

 The unique property of influenza virus is its potential for emergence of new strains of epidemic and pandemic potential. This occurs due to antigenic variation in the new strain. Therefore, it is important to understand the genetic changes that occur in influenza virus.

Reassortment: The segmented genome of influenza virus makes this phenomenon possible. The process of reassortment can occur when infection with two different influenza virus strains occurs inside one cell. Ideally each virus should produce its own progeny with identical genetic content. But, during the process of assembly, there is a possibility that the genome segments of one virus may get assembled inside the other virus. This results in production of a new virus with genetic component that is different from the parent virus (Fig. 2). The reassortant virus is important because of its new genetic makeup. This is affected most when the genome segment encoding the surface proteins such as hemagglutinin or neuraminidase is different than the parent strain, as antibodies against these proteins are responsible for host immunity.

Fig2. Reassortment (schematic)

Reassortment occurs within influenza virus types (genus) but not between different genera or types. This means it occurs within the members of influenza A or B or C, but not between influenza A, B and C. Most commonly it is seen in influenza A.

Example: Influenza A (H1N1)pdm09 virus which was the latest pandemic influenza virus is a reassortant virus of 4 different strains consisted of North American avian strain, Eurasian swine strain, human H3N2 and classic swine strains. The reassortant virus of first three was already circulating amongst the North American swine which form the new reassortant virus with classic swine strain.

Recombination: In this, the genetic material of each segment comes from multiple origins.

Role of Antigenic Variation in Influenza Virus Epidemiology

 Antigenic drift: This is caused by accumulation of point mutations leading to gradual change of antigenicity. The immunological pressure to surface proteins HA and NA is mainly responsible for point mutation. The resulting antigenic change in drift virus is minor, but sufficient enough to overcome the immune response produced by the vaccine strain. The appearance of drift strain thus makes the population susceptible. This in turn requires the change in vaccine strain in every few years.

Antigenic drift is more commonly observed in human influenza virus than avian strains, possibly because of constant immunological pressure from the humans than birds.

Antigenic shift: Sudden emergence of influenza virus with a major antigenic change than the previously circulating strains occurs due to antigenic shift. This can occur by various processes:

 • Genetic reassortant between two different influenza viruses leading to emergence of a novel virus (1957, 1968 and 2009 pandemics).

• Antigenic change in avian/non-human strain that makes it capable of infecting humans with the ability to spread (For example, 1918 pandemic by avian influenza like strain).

• Re-emergence of previously circulating virus in an immunologically naïve population (e.g. 1977 pandemic).

Maintenance of Influenza Virus in Nature

 Influenza A: Of the 18 HA and 11 NA subtypes, aquatic birds are the natural reservoir of all types of influenza A viruses except H17N10 and H18N11 which have been detected only in bats. Aquatic birds do not manifest the disease. Ducks, shore birds and gulls are the main reservoir. Replication of virus occurs mainly in the intestinal tract of birds and virus gets excreted in the fecal matter. Transmission of virus amongst the aquatic birds occurs by ingestion of contaminated water.

Besides the water birds, several wild and domestic bird species also can get infected with influenza virus. These birds are chicken, turkey, ducks, geese, quail, sea birds, shore birds, gulls. Infection may be asymptomatic in some avian species while symptomatic in some others species. Water birds are usually resistant and do not manifest with symptoms.

Influenza A virus can also infect human, swine, horses, dogs and several other mammals.

Influenza A virus subtypes that have established themselves in various hosts (Table1).

Influenza B virus infects mostly human host, also has been isolated in seals.

Influenza C virus infects human, swine and dogs.

Influenza D virus can infect swine, cattle, sheep and goat. Cattle have been shown as the natural reservoir.

Table1. Influenza A virus subtypes in various hosts

Determinants of Host Range Specificity

 All known HA and NA types of influenza A virus infect the avian species, only a few of them infect other animals including man. This indicates that influenza A viruses broadly maintain a host range restriction.

Hemagglutinin (HA) glycoprotein is one of the major determinants of the host range restriction because of its capability of recognizing the host cell receptor, sialyloligosaccharide.

Human influenza virus binds preferentially to sialyloligosaccharide terminated by N-acetyl sialic acid linked to galactose by a-2, 6 linkage, the receptors that are predominantly present in humans. Until now, only a few HA types: H1, H2 and H3 have been found to infect human host.

Influenza virus infecting birds binds preferentially to the sialyloligosaccharide receptor having a-2, 3 linkage between sialic acid and galactose. These strains are called avian influenza virus. All HA types can bind to receptor having a-2, 3 linkage between sialic acid and galactose. So, avian species can be infected by all HA types of influenza A virus.

Influenza virus infecting pigs binds to the sialyloligosaccharide receptor having a-2, 3 linkage or a-2, 6 linkage between sialic acid and galactose. As pigs possess both types of receptors, they can be infected by both avian and human influenza viruses. Therefore, pigs are considered as “mixing vessel” and provide the scope for reassortant and emergence of novel strains.

Neuraminidase (NA) also shows host restriction by its preference for particular type of sialic acid linkage in specific host. Avian viruses cleave sialic acid of a-2, 3 linkage and human viruses cleave sialic acid of a-2, 6 linkage. Certain NA type of avian virus when infects human host, adapts to cleave sialic acid of a-2, 6 linkage in addition to a-2, 3 linkage.

اخر الاخبار

اخبار العتبة العباسية المقدسة

مركز تصوير المخطوطات وفهرستها.. جهود منهجية لتصوير التراث وحفظه

قسم التطوير يواصل تقديم دورة أخلاقيات المهنة ضمن البرنامج التأهيلي للمنتسبين الجدد

انطلاق فعاليات الجلسة المسائية لمسابقة النور القرآنية الدولية الجامعية في جامعة العميد

الحزام الأخضر الجنوبي الأول يستضيف وفدًا من محافظة البصرة ضمن نشاطات قسم الشؤون الفكرية والثقافية

المزيد

الآخبار الصحية

أول إرشادات غذائية قائمة على الأدلة لمعالجة الإمساك المزمن

صباح بلا إفطار؟.. صحتك في خطر!

هل يمكن للجلد أن يكشف عن صحتك العقلية؟.. دراسة حديثة تجيب

السر في مطبخك.. 6 أطعمة تمنح عظامك قوة الشباب

المزيد

الآخبار التكنلوجية

ناسا تكشف: كوكب الأرض أصبح أقل لمعانا خلال العقود الماضية

دراسة: الوقت الذي تستخدم فيه هاتفك قد يفضح حالتك النفسية

علماء يحذرون: عمر الأب يحدد صحة الجنين

الهنغاري لاسلو كراسناهوركاي يفوز بجائزة نوبل للآداب 2025

المزيد

مواضيع ذات صلة

Chikungunya virus

West Nile virus

Transmission Cycle of Japanese encephalitis virus

Lab Diagnosis of Dengue virus

Pathogenesis of Dengue virus

Rotavirus

Mumps virus

Morbillivirus

Viral Characteristics of Human immunodeficiency virus (HIV)

Rubeola (Measles)

DNA Tumor Viruses

Rhabdoviridae