An influenza A virion is composed of the nucleocapsid, a surrounding layer of the matrix protein 
(M1) and the membrane envelope. The envelope contains two major surface glycoproteins, i.e. hemagglutinin 
(HA) and neuraminidase 
(NA), and a minor membrane protein M2
. The nucleocapsid consists of individual ribonucleoproteins 
(vRNPs). Each vRNP contains one of the 8 genomic negative sense RNA segments (vRNA), multiple copies of the major structural protein NP 
, and a few copies of the RNA dependent-RNA-polymerase complex (not shown). All 8 vRNA species must be present in an infectious virion.
A virion attaches to the host cell membrane via HA and enters the cytoplasm by receptor-mediated endocytosis (STEP 1), thereby forming an endosome. A cellular trypsin-like enzyme cleaves HA into products HA1 and HA2 (not shown). HA2 promotes fusion of the virus envelope and the endosome membranes. A minor virus envelope protein M2 acts as a ion channel thereby making the inside of the virion more acidic. As a result, the major envelope protein M1 dissociates from the nucleocapsid and vRNPs are translocated into the nucleus (STEP 2) via interaction between NP and cellular transport machinery. In the nucleus, the viral polymerase complexes transcribe (STEP 3a) and replicate (STEP 3b) the vRNAs. Newly synthesized mRNAs 
migrate to cytoplasm (STEP 4) where they are translated. Posttranslational processing of HA, NA, and M2 includes transportation via Golgi apparatus to the cell membrane (STEP 5b). NP, M1, NS1 (nonstructural regulatory protein - not shown) and NEP (nuclear export protein, a minor virion component - not shown) move to the nucleus (STEP 5a), where bind freshly synthesized copies of vRNAs. The newly formed nucleocapsids migrate into the cytoplasm in a NEP-dependent process and eventually interact via M1 with a region of the cell membrane, where HA, NA and M2 have been inserted (STEP 6). Then the newly synthesized virions bud from infected cell (STEP 7). NA destroys the sialic acid moiety of cellular receptors, thereby releasing the progeny virions.
Although influenza viruses have been extensively studied for years, some aspects of their replication (especially morphogenesis) remain poorly understood.
Influenza A virus genome
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M1, matrix protein. Surrounds the core (nucleocapsid) and links it with viral envelope; a product of vRNA7. Plays a central role in virus morphogenesis.
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HA, hemagglutinin, a major viral surface glycoprotein; mediates virus attachment to the cell by binding sialic acid-containing receptor; the product of vRNA4. Its cleavage product (H2) mediates membrane fusion. HA undergoes complex posttranslational modifications and exists as a trimer. Antibodies to HA neutralize the virus infectivity, but the variability of this protein allows the virus to overcome host's immune defence.
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NA, neuraminidase, viral surface protein; the product of vRNA6. Exists as a tetrameric glycoprotein. NA destroys the sialic acid moiety of cellular receptors thereby releasing the newly synthesized virions. Synthetic sialic acid analogs working against NA soften flu symptoms and shorten duration of illness.
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M2, small integral membrane protein; ion channel; translated from a spliced product of vRNA7. The target for antivirus drugs amantadine and rimantadine.
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Viral ribonucleoprotein (vRNP), a viral nucleocapsid component, consists of one minus-strand vRNA segment, multiple copies of major structural protein NP and a few copies of RNA dependent-RNA-polymerase complex. The vRNA segments are circularized by base-pairing between their 3' and 5' ends (not shown). vRNA segments 1 through 6 code for one protein each. These are cap-binding polymerase subunit PB2, catalytic polymerase subunit PB1 and polymerase subunit PA associated with the protease activity (none is shown), HA, NP and NA. vRNA segment 7 codes for 2 proteins, M1 and M2. These two proteins share 8 N-terminal amino acid residues, because M2 is translated from spliced M1 mRNA. Likewise, vRNA segment 8 also codes for 2 proteins, nuclear non-structural regulatory protein NS1 and the nuclear export protein NEP, also known as NS2 (translated from the spliced NS1 mRNA).
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NP, nucleoprotein, RNA-binding protein, a component of viral transcriptase complex; involved in nuclear/cytoplasmic transport of vRNA; the product of vRNA5.
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All viral mRNAs possess the cap structure derived from host-cell RNA and the 3' poly(A).
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