**1. Introduction**

Influenza virus is a perpetual economic burden that causes a significant morbidity and mortality rate in humans. Globally, the reported cases of seasonal influenza viruses (SIVs) rise up to 3–5 million during epidemics with an estimated death toll of 290,000–650,000 per year [1]. The Global Influenza Surveillance and Response System (GISRS), a surveillance system of the World Health Organization (WHO), analyses the incidences of avian and zoonotic influenza virus to accurately estimate the severity of the disease. As of March 5–18, 2018, GISRS-WHO has reported 46.8% cases of influenza A virus (where 64% were influenza A(H1N1)pdm09 cases and 36% were infected with H3N2) and 53.2% of influenza B virus (where 91% were B-Yamagata strain and 9% were B-Victoria) [2]. The co-morbidity condition (such as diabetes, heart or liver disease) or the immuno-compromised condition of patients is the predominant cause of mortality associated with influenza virus.

Influenza virus belongs to the *Orthomyxoviridae* family and is categorized as influenza A virus (IAV), influenza B virus (IBV), and influenza C virus (ICV). The genome of influenza virus is segmented with 8 negative-sense single-stranded viral RNA (vRNA) strands which code for 11 proteins in cases of IAV and IAB, whereas IAC has seven vRNA segments that code for nine proteins. These segments are named after their main proteins such as segment 1-PB2 (polymerase basic 2), segment 2-PB1 (polymerase basic 1), segment 3-PA (polymerase acid), segment 4-HA (hemagglutinin), segment 5-NP (nucleoprotein), segment 6-NA (neuraminidase), segment 7-M (matrix), and segment 8-NS (non-structural) [3]. Influenza vRNA has heterotrimeric RNA-dependent RNA polymerase (RdRp) at the 5′ and 3′ end of the segment

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

and the internal part of vRNA is bound with several nucleoproteins (NP) forming viral ribonucleoprotein complexes (vRNP) [4]. Hemagglutinin (HA) and neuraminidase (NA) are envelope glycoproteins responsible for the antigenic variation and the generation of different strains of influenza virus. HAs are of 16 subtypes (H1–H16) and NA has nine subtypes (N1- N9) [5]. As a result of the antigenic drift, SIVs are generated due to several point mutations in the *HA* and *NA* genes caused by RdRp [6]. Thus, the antibodies generated during primary infection with the influenza virus are unable to neutralize the drifted strains of SIVs, leading to epidemics or pandemics. Considerable numbers of individuals are always at risk of getting infected with influenza viruses, thus creating a state of alertness. In addition to SIVs, there are several pandemic viruses generated due to the antigenic shift, where the newly drifted strains of viruses have the ability to cross species barriers, as a result of the re-assortment of a viral genome with other influenza viruses (human or non-human).

cats, pigs, horses, ferrets, seals, and whales (**Figure 1**). Avian IAV such as H5N1 and H9N2 are known to cause bird flu, whereas H1N1 and H3N2 are responsible for swine flu. IAVs are also categorized as seasonal and pandemic based on genetic variation and the severity of influenza disease; IAV transmission occurs by direct or indirect contact, inhaling virus-infected droplets or small droplet nuclei, being exposed to diseased poultry, feeding raw or undercooked poultry, transplacental transmission, or drinking water contaminated by viruses [7]. The serological evidence validated that human-to-human transmission of influenza viruses is inefficient; however, in some rare cases human-tohuman transmission was observed during an outbreak of the highly pathogenic avian influenza viruses (HPAI) of H5N1 [8]. Influenza virus enters the human body through the respiratory tract and its incubation period is 1–7 days. The common symptoms associated with influenza are respiratory distress, fever, headache, cold, abdominal pain and joint pain [9]. With the progression of the disease, other symptoms observed are bloody sputum and pneumonia that further cause respiratory failure leading to acute respiratory distress syndrome (ARDS) [10]. IAV-infected patients can be diagnosed by reverse transcription-polymerase chain reaction (RT-PCR), viral culture, and the high levels of

Introductory Chapter: Human Influenza A Virus Infection - Global...

http://dx.doi.org/10.5772/intechopen.77350

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The IAV enters in the host cell by binding with surface receptors possessing sialic acid moiety. Viruses are internalized by endocytosis and the uncoating of the virus by matrix protein 2, an ion channel. The vRNA is released in the cytoplasm and is imported to the nucleus where vRNA is transcribed and replicated by using its polymerase [11]. Thus, these steps lead to the synthesis of a positive sense complementary RNA (cRNA) and viral messenger RNA (vmRNA) with 5'cap and 3′ poly (A) tail. The influenza virus polymerase does not exhibit capping activity at the 5'end; hence, they have to depend on host-capped mRNAs where they capture its 5'cap, a process known as cap snatching [12]. The viral m-RNA is translated in the cytoplasm after being exported from the nucleus and viral proteins, and nucleoproteins are synthesized by cellular ribosomes. Translated viral proteins re-enter the nucleus and bind to the vRNAs to generate viral ribonucleoproteins (vRNPs). Following nuclear export, progeny vRNPs and viral proteins are assembled to form virions

The prominent IAVs causing pandemics and outbreaks in various parts of the world are shown in the **Figures 2** and **3**, respectively. The 1918 spread of human influenza A(H1N1) virus has caused death of approximately 40–50 million people worldwide. This virus had again emerged in 2009 and caused a death toll of 4100 people. The clinical presentations were similar to the earlier strain that led to a less severe response. The twenty-first-century influ-

HA antigen- specific neutralizing antibodies.

**3. Life cycle of influenza A virus**

which later egress from the host cell.

**4. Pandemics and outbreaks of human influenza A virus**

enza viruses that cause infections in humans are briefly discussed below.
