Influenza Virus

Influenza viruses belong to the family Orthomyxoviridae, a family that represents enveloped viruses, the genome of which comprises segmented negative, single-strand RNA segments. People have had flu for thousands of years. It is speculated that humans may contract the flu at the beginning of domesticating animals. The development of agriculture and the establishment of permanent settlements provided numerous potential hosts that can cause epidemics. The word "flu" came from an Italian in the mid-17th century to describe a disease caused by miasma. The human influenza virus was not isolated until 1933.

Classification

Influenza viruses are mainly divided into three species: influenza A virus, influenza B virus, and influenza C virus. Only type A and B are clinically relevant to humans. Although both viruses can cause human infection, genera A typically leads to widespread illness and epidemics.

Influenza A virus

It was successfully isolated in 1933. Influenza A virus is commonly carried by animals such as birds, pigs, and is a pathogenic agent of zoonotic infections. Only influenza type A viruses are known to have caused pandemics. Influenza A virus undergoes an antigenic shift, which is a sudden change in antigenicity resulting from genetic recombination between viral strains, producing a new virus subtype. Based on the properties of the surface proteins hemagglutinin (H) and neuraminidase (N), influenza A viruses are subclassified and named by combining the H and N numbers, such as A(H1N1), A(H3N2).
Influenza B virus

Type B was obtained in 1940. It is only found in humans and usually causes milder symptoms than type A virus. Although it can trigger seasonal illness and human epidemics, influenza B virus has not caused a pandemic. Influenza B viruses are further classified into two lineages: B/Yamagata and B/Victoria.
Influenza C virus

Type C infections generally cause mild illness and are not thought to cause human flu epidemics.

Structure

Influenza A and B viruses are virtually indistinguishable by electron microscopy. They are typically spherical with a diameter of about 100 nm, but sometimes are filamentous with a length usually exceeding 300 nm. The outermost layer of influenza virus particles is the host cell-deriving envelope. The envelope is embedded with glycoprotein spikes of hemagglutinin (HA) and neuraminidase (NA), protruding from the envelope. Both HA and NA determine the subtypes of the influenza virus. The ratio of HA to NA is about 4:1. Less matrix ion channels M2 spans the lipid envelope. The matrix protein M1 is beneath the envelope and encapsulates the core of the virion.

Inward the virion is the viral genome composed of 8 pieces of single-stranded RNA (only type A and B). The RNA, coated with nucleoprotein and heterotrimeric RNA-dependent RNA polymerase (three subunits: PB1, PB2, and PA), is assembled into a helical ribonucleoprotein (RNP) complex. Nuclear export protein (NEP) is also found in the interior of the virion.

Figure 1.

Target	Protein	Description
HA	Hemagglutinin	The HA protein is processed into HA1 and HA2 by serine proteases during viral replication, which gives virus infectivity. The HA2 is involved in the fusion of viral envelope with host cell membrane, while the HA1 contains the receptor binding and antigenic sites. It is also an antigen that can be recognized by the immune system.
NA	Neuraminidase	It is capable of destroying receptor, cleaving terminal sialic acid residues from cell-surface glycoproteins and gangliosides to release offspring virus from the host cell. Additionally, the NA also removes sialic acid residues from the virus envelope, blocking the aggregation of viral particles to enhance infectivity.
M1	matrix protein M1	M1 interacts with both viral RNA and nucleoprotein, bringing them together within the RNP complex. It also associates with NEP, mediating the M1-RNP export via nucleoporins into the cytoplasm.
M2	matrix ion channels M2	It is the target of the amantadine class of anti-influenza drugs, which inhibit ion channel activity and prevent virus from unshelling. As a surface protein, it can be a vaccine component.
NEP/NS	Nuclear export protein	NEP, together with M1, is involved in the translocation of M1-RNP into the cytoplasm.
NP	Nucleoprotein	Viral RNA is packaged with nucleoprotein into a helical ribonucleoprotein complex.
RNP	Ribonucleoprotein	The RNA, coated with nucleoprotein and heterotrimeric RNA-dependent RNA polymerase (three subunits: PB1, PB2, and PA), assembls into a helical ribonucleoprotein (RNP) complex.

The Influenza Pandemic Event

In 1918-1920 Spanish Flu, more than 50 million people died of H1N1 influenza worldwide. About 1.5 to 2 million people died in the 1957-1958 Asian flu pandemic, which was caused by the H2N2 influenza A subtype. The H3N2 led to the 1968-1969 Hong Kong Flu, causing 1million deaths. The bird flu panic of 2006 was caused by a strain of Influenza A. The swine flu of 2009 caused a great deal of widespread sickness and fear. This was a new strain of influenza A called H1N1 and was carried by pigs but quickly spread through humans. The 2009 Swine Flu was spread to 208 countries and caused approximately 18000 deaths. The pandemic of H7N3 avian influenza in Mexico in late 2012 was the largest ever outbreak in poultry in North America, with 20 million birds killed. And influenza has become a typical seasonal flu and causes about 290000 to 650000 deaths annually around the world.

Transmission

Influenza is a typical seasonal diseases and frequently occurs in spring and winter. There are three transmission routes of influenza virus.

Through aerosol infection

The influenza virus is mainly transmitted by aerosol infection. For example, large droplets (larger 5 μm in diameter) produced when talking, coughing, or sneezing enters the mucous membrane through short-distance contact.
Through aerogenic transmission

Propagation may occur in tiny droplet cores (smaller 5 μm in diameter) that can stay in the air for longer periods.
Through direct contact

Direct contact with virus-contaminated surfaces (such as handshaking) and subsequent oral and nasal contact can cause transmission. Isolation and identification of virus

Related Proteins

Uniprot No.	Species	Product Name
Q0HD60	H1N1	Recombinant Influenza A virus Hemagglutinin (HA), partial
P88838	H7N7	Recombinant Influenza A virus Neuraminidase (NA), partial
P69291	H3N2	Recombinant Influenza A virus Nucleoprotein (NP)
Q9IQ47	H3N2	Recombinant Influenza A virus Polymerase acidic protein (PA), partial
Q0HD54	H1N1	Recombinant Influenza A virus Non-structural protein 1 (NS)
A4GCL0	H1N1	Recombinant Influenza A virus Matrix protein 1 (M)
A4GCM0	H1N1	Recombinant Influenza A virus Matrix protein 2 (M), partial
P0C0U1	H1N1	Recombinant Influenza A virus Protein PB1-F2 (PB1)
P12445	H7N1	Recombinant Influenza A virus Polymerase basic protein 2 (PB2), partial
A8C8X2	H1N1	Recombinant Influenza A virus Putative protein PB1-F2 (PB1-F2)
P04665	Influenza B virus	Recombinant Influenza B virus Nucleoprotein (NP)
P03502	Influenza B virus	Recombinant Influenza B virus Non-structural protein 1 (NS)
P68760	Influenza B virus	Recombinant Influenza B virus Hemagglutinin (HA)
P67907	Influenza B virus	Recombinant Influenza B virus Neuraminidase (NA), partial
P13875	Influenza B virus	Recombinant Influenza B virus Polymerase basic protein 2 (PB2), partial
P13880	Influenza B virus	Recombinant Influenza B virus Matrix protein 1 (M)
P11136	Influenza B virus	Recombinant Influenza B virus Polymerase acidic protein (PA), partial
P13872	Influenza B viru	Recombinant Influenza B virus RNA-directed RNA polymerase catalytic subunit (PB1), partial
P13881	Influenza B virus	Recombinant Influenza B virus Matrix protein 2(M), partial