Influenza A virus, commonly known as the flu, is a respiratory pathogen that causes seasonal epidemics and occasional pandemics. Its genetic material, ribonucleic acid (RNA), contains all the instructions for replication and spread. This genome dictates its structure, ability to infect cells, and immune evasion.
Understanding Influenza A RNA
Its genome consists of single-stranded, negative-sense RNA, which cannot be directly translated into proteins upon entering a cell. The viral RNA is segmented into eight distinct pieces, each encoding specific viral proteins. These segments are packaged together within the viral particle.
Each segment carries genes for different viral components. For example, two segments encode the surface proteins hemagglutinin (HA) and neuraminidase (NA), important for viral entry and release from host cells. Other segments code for internal proteins like nucleoprotein (NP), matrix proteins (M1 and M2), and non-structural proteins (NS1 and NS2). Segments also encode polymerase complex proteins (PB2, PB1, and PA), responsible for replicating viral RNA.
How Influenza A RNA Replicates and Infects
The replication cycle of influenza A begins with the virus attaching to the surface of a host cell, typically in the respiratory tract. The hemagglutinin protein on the viral surface binds to sialic acid receptors on the host cell membrane. The host cell then engulfs the virus via receptor-mediated endocytosis, enclosing it within an endosome.
Once inside the endosome, the acidic environment triggers a change in the viral hemagglutinin, leading to the fusion of the viral envelope with the endosomal membrane. This fusion releases the viral ribonucleoprotein complexes (vRNPs) into the host cell’s cytoplasm. These vRNPs are then transported into the host cell’s nucleus, a unique step for an RNA virus.
Inside the nucleus, the viral RNA-dependent RNA polymerase begins its work. Since the viral RNA is negative-sense, it first transcribes positive-sense messenger RNA (mRNA) from the viral RNA segments through a process called “cap-snatching”. This viral mRNA is exported to the cytoplasm for translation into viral proteins by host ribosomes. The viral polymerase also replicates the negative-sense viral RNA segments, using positive-sense complementary RNA (cRNA) as a template for new genome copies.
Newly synthesized viral proteins and RNA segments are transported to the cell membrane for assembly. The viral RNA segments, nucleoproteins, and polymerase proteins gather to form new vRNPs. These vRNPs move to the host cell’s plasma membrane, where they are packaged into new viral particles. The virus buds off from the host cell membrane, acquiring its outer envelope containing HA, NA, and M2 proteins, and is released to infect other cells. The entire replication process can take approximately eight hours, ultimately leading to the death of the infected host cell.
Influenza A RNA and Public Health
The segmented RNA genome and error-prone RNA polymerase of influenza A have public health implications. One consequence is antigenic drift, which refers to small, continuous changes in influenza virus genes. These mutations primarily occur in the genes encoding the hemagglutinin (HA) and neuraminidase (NA) surface proteins. The viral RNA polymerase lacks a proofreading mechanism, leading to a high rate of point mutations during replication. These gradual changes can alter the antigenic properties of the virus, making existing antibodies less effective and necessitating annual updates to influenza vaccines.
Antigenic shift, a more dramatic change, also arises from the segmented RNA genome. This occurs when a single cell is co-infected by two different influenza A virus strains, allowing exchange of entire RNA gene segments. This process, called reassortment, can result in a completely new influenza A virus subtype with novel HA and/or NA proteins. Since human populations often have little to no pre-existing immunity to these newly reassorted viruses, antigenic shift can lead to widespread pandemics.
Understanding these genetic characteristics of influenza A RNA directly informs public health strategies, particularly vaccine development and surveillance. Scientists constantly monitor circulating influenza strains for new mutations and reassortment events to predict which strains are most likely to cause widespread illness in the upcoming flu season. This ongoing surveillance is important for selecting appropriate viral strains for the annual influenza vaccine, aiming to provide the best protection against the evolving virus.