Minus-Strand RNA Viruses: RNA-Dependent RNA Polymerase Is Part of Influenza Virus

After reading this section, you should be able to

■ Describe in general terms the strategy used by minus-strand RNA viruses to synthesize their nucleic acids and proteins

■ Explain how having a segmented genome impacts synthesis of viral mRNA and proteins and the generation of new strains of a virus

■ Create a flow chart that summarizes the life cycle of influenza virus, noting the specific mechanisms it uses to accomplish each step of its life cycle

Negative-strand viruses are found in many families, including Rhabdoviridae (e.g., rabies virus), Filoviridae (e.g., Marburg and Ebola viruses), Paramyxoviridae (e.g., measles and mumps viruses), Bunyaviridae (e.g., hantaviruses), and Orthomyxoviridae (e.g., influenza viruses).

Most negative-strand RNA viruses are enveloped viruses that infect plants and animals. They vary in morphology from spherical, to filamentous, rod-shaped, bulletshaped, and pleomorphic. Members of four families have nonsegmented linear genomes and are grouped into the order Mononegavirales.

The remaining negative-strand RNA viruses have segmented genomes that range from two to eight segments, each encoding usually one protein. The genomes of negative-strand RNA viruses cannot function as mRNA. Therefore these viruses must bring at least one RNA-dependent RNA polymerase into the host cell during entry.

Initially the viral genome serves as the template for mRNA synthesis (figure). Later the virus switches from mRNA synthesis to genome replication, as the RNA-dependent RNA polymerase synthesizes a distinct plus-strand RNA for replication.

During this phase of the life cycle, the plus-strand RNA molecules synthesized from the minus-strand genome serve as templates for the manufacture of new negative-strand RNA genomes. Our focus in this section is on influenza viruses.

Influenza Virus
Influenza Virus

Schematic representation of an influenza A virus showing the double helical hairpin RNA genome. The protein or proteins encoded by each RNA segment are shown below each nucleocapsid. A protein called M1 (lavender; M stands for matrix) lines the lipid bilayer envelope (dark blue).

Another matrix protein (M2) is embedded in the envelope. NS proteins (NS1 and NS2) are nonstructural proteins that function in the life cycle of the virus but are not part of the virion.

Influenza Virus

There are three types of influenza virus: influenza viruses A, B, and C. Influenza virus virions are composed of an envelope enclosing seven or eight nucleocapsids, depending on the type of influenza virus. Each nucleocapsid consists of a single, negative-strand RNA that exists as a double helical hairpin (figure).

Formation and maintenance of the double helix does not involve base pairing. Rather, this is accomplished by numerous copies of the nucleocapsid protein (NP), which coat the RNA. The three proteins of the influenza polymerase (PA, PB1, PB2) are attached to the open end of the hairpin.

An influenza virion enters a host cell by receptor-mediated endocytosis. This encloses the virus in an endosome (figure 27.28b). When the endosomal pH decreases, a conformational change in the virion facilitates contact with the endosome membrane, allowing fusion of the endosome membrane and viral envelope to occur, releasing the nucleocapsids into the cytosol.

Influenza (flu; section) Once the RNA segments and associated RNA-dependent RNA polymerase enter the host cell nucleus, the genome segments serve as templates for mRNA synthesis (figure)

Influenza Virus and Its Life Cycle
An Influenza Virus and Its Life Cycle

This simplified version of the influenza life cycle omits several steps and represents the viral RNA molecules as simple lines.

Negative-strand RNA is red and positive-strand RNA is green. After entry by receptor-mediated endocytosis, the virus envelope fuses with the endosome membrane, releasing the nucleocapsids into the cytosol.

The nucleocapsids enter the nucleus, where synthesis of viral mRNA and genomes occurs. The influenza virus polymerase is composed of three subunits. PB1 has RNA-dependent RNA polymerase activity.

PB2 is an endonuclease responsible for the cap snatching described in step 1. PA is a protease.

An Influenza Virus and Its Life Cycle

step 1). Later the virus switches from mRNA synthesis to genome replication. During this phase of the life cycle, the plusstrand RNA molecules synthesized from the minus-strand genome segments serve as templates for new negative-strand RNA genomes (figure step 4).

Virions exit the host cell by budding and thus acquire their envelope (figure step 6; s)

Key Concepts

Minus-Strand RNA Viruses: RNA-Dependent RNA Polymerase Is Part of the Virion

■ For minus-strand RNA viruses to synthesize mRNA and replicate their genomes, their virions must carry an RNAdependent RNA polymerase, which enters the host cells as the genome does.

■The polymerase first synthesizes mRNA from the negative-strand genome. Later it is used to replicate the genome by way of a plus-strand intermediate (figure ).

■ Influenza viruses have segmented genomes; most segments encode a single protein. The viruses exit by budding (figure).

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