+Overview of Influenza Replication

The influenza virus has a negative sense RNA genome. In order to replicate, this means that the virus must first produce positive sense mRNA in order to produce necessary enzymes. Once the enzymes are translated, replication can take place. Positive sense cRNA is then made from the original negative sense RNA, using the enzymes. Negative sense RNA progeny are then made from the positive sense cRNA. The final viral progeny eventually bud from the host cell, ready to infect other cells.

+Influenza Replication in Greater Detail

The influenza virus enters the host cell by having its hemagglutinin bind to the sialic acid found on glycoproteins or glycolipid receptors of the host. The cell then endocytoses the virus. In the acidic environment of the endosomes, the virus changes shape and fuses its envelope with the endosomal membrane. This is followed by a signal to release the virus nucleocapsid into the host cytoplasm. From there, the nucleocapsid travels to the host nucleus.

In the host nucleus, the virus does primary transcription to produce necessary proteins for replication. The primary transcription involves what is known as "cap snatching." What this means is that the viral endonuclease (PB2) cuts the 5' methylguanosine cap as well as ten to thirteen nucleotides from the RNA. This is then used as the primer for the transcription of the protein PB1, a viral transcriptase. In influenza A and B, ten proteins result from the translation of the eight segments of the genome, including hemagglutinin, neuraminidase, PB1, PB2, nucleoprotein, another RNA polymerase complex, two matrix proteins, and two NS proteins.

Once the initial proteins are made, then eight complementary positive sense RNA strands are made from the eight negative sense RNA segments (at least in influenza A and B. . . influenza C has seven segments). These lack the 5' capped primer, as well as the 3' poly (A) tail found in the mRNA. From this cRNA, a negative sense RNA is produced. Various proteins then help this negative sense RNA exit the nucleus and into the cytoplasm of the host.

In the meanwhile, in the cytoplasm, the hemagglutinin and neuraminidase have undergone glycosylation, polymerization, and acylation. The hemagglutinin, neuraminidase, and the matrix protein two (M2) all travel together to the plasma membrane. There the proteins meet with the other matrix protein (M1), and begin the budding process. At least eight RNA segments come to the site (the mechanism is not completely known), and the virus buds. The neuraminidase finally destroys the sialic acid receptors on the membrane, thus allowing the virus to leave the cell.


From Robert A. Lamb and Robert M. Krug's "Orthomyxoviridae: The Viruses and Their Replication," in Fields Virology, Lippincott-Raven Publishers. 1996. p 1370.

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