Introduction to Molecular Biology: From Cells to Atoms - Anthony Rees, Michael Sternberg 2002

Cells and Viruses
RNA-containing Viruses

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Fig. 5.1.

RNA-Containing Viruses lack DNA; the Genetic information of these viruses is encoded in RNA. The RNA may be single- or double-stranded, and the host Cell may be prokaryotic or eukaryotic. Only single-stranded RNA viruses infect Bacteria, whereas PLANT AND ANIMAL viruses can be either single- or double-stranded.

Double-stranded RNA viruses infect both plants and animals. For example, Colorado tick fever virus and rice dwarf virus infect insects and plants, respectively. These viruses contain RNA in a segmented form: as A number of double-stranded fragments.

Single-stranded RNA viruses can be divided into two types: plus-strand and minus-strand. In the first type, the RNA strand can function directly as mRNA within the host cell, whereas In the second type, a plus-strand must first be generated from the minus-strand using cellular RNA polymerases. Animal viruses occur in both types, while the majority of plant viruses belong to the plus-type. A special class of plus-single-stranded viruses is formed by Retroviruses, which are capable of infecting exclusively animal Cells. They differ from other RNA-containing viruses in having a diploid genome consisting of two identical plus-RNA strands. As Examples of single-stranded RNA-containing viruses, Influenza virus, tobacco mosaic virus, and retroviruses will be discussed below.

REOVIRUSES are non-enveloped icosahedral viruses whose protein capsid consists of two layers—an outer and an inner layer. Inside the capsid are 10 or 11 segments of double-stranded RNA.

The infectious process begins with the penetration of RNA into The Cell and then proceeds according to scheme 1 (see Fig. 5.2). Following partial degradation of the outer capsid by lysosomal Enzymes, the RNA within the resulting subviral particle is transcribed; its copies leave the particle and attach to Ribosomes. Subsequently, the host cell produces the Proteins required for the assembly of new Viral Particles.

Fig. 5.2. GENERALIZED SCHEME OF reproduction of RNA-containing viruses.

Viral RNA Replication occurs via a conservative mechanism—unlike the replication in DNA-containing organisms, which is semi-conservative (Ch. 20). One strand of each RNA segment serves as a template for the synthesis of A large number of new plus-strands. Minus-strands are then generated on these plus-strands as templates; the plus- and minus-strands do not separate in the process, but remain together as double-stranded molecules. The assembly of new viral particles from newly formed plus- and minus-segments and capsid proteins is somehow associated with the mitotic spindle of the host cell, although the exact assembly mechanism remains unknown.

INFLUENZA VIRUS is an example of a minus-single-stranded RNA virus. It possesses an envelope and a helical core. The latter consists of eight segments of minus-RNA, which form Helical structures in complex with proteins. Each segment encodes one of the viral proteins. The virus contains the matrix protein in the largest quantity, located on the inner side of the envelope to provide structural stability. All envelope proteins are encoded by viral RNA, whereas the Lipids are of cellular origin (see "DNA-containing viruses", section "Assembly"). The main envelope proteins are hemagglutinin and neuraminidase.

The infectious process, proceeding according to scheme 1 (see Fig. 5.2), begins with the attachment of the virus to the host cell surface via hemagglutinin. This is followed by the fusion of the envelope with The cell membrane; the nucleoprotein core (nucleocapsid) enters the cell, and the virus-encoded RNA-dependent RNA polymerase synthesizes plus-mRNA strands on the viral minus-strands, after which viral proteins are produced on the host cell ribosomes. Some of these proteins play a crucial role in the replication of the viral genome.

Replication takes place in The Nucleus, where minus-RNA strands are synthesized using the same, albeit likely modified, RNA-polymerase. After nucleocapsid proteins enter the nucleus, nucleocapsid assembly takes place. The nucleocapsid then passes through the Cytoplasm, acquiring envelope proteins along the way, and exits the cell by budding from its Plasma Membrane. Neuraminidase is thought to be involved in the budding process.

TOBACCO MOSAIC VIRUS is an example of a single-stranded plant virus. This non-enveloped helical virus contains 2,130 identical capsid protein molecules and a single RNA strand. The RNA is located in a helical groove formed by protein subunits and is held in place by numerous weak bonds.

The infectious process, proceeding according to scheme 1 (see Fig. 5.2), consists of the virus penetrating The plant cell followed by the rapid loss of its capsid. Subsequently, As a result of the direct Translation of the plus-stranded viral RNA by the host cell ribosomes, several proteins are produced, some of which are required for the replication of the viral genome.

Replication is carried out by RNA replicase, which produces RNA copies for new virions. Capsid Protein Synthesis occurs only after the infecting RNA undergoes a certain modification that enables the attachment of cellular ribosomes to the region of the RNA that encodes this protein. Virion assembly begins with The formation of discs from the capsid protein. Two such protein discs, arranged concentrically, form a biscuit-like Structure, which assumes a helical shape upon binding to RNA. The subsequent addition of protein molecules continues until the RNA is completely covered. In its final form, the virion is a cylinder 300 nm in length.

RETROVIRUSES belong to the plus-single-stranded RNA-containing animal viruses; almost all of them are oncogenic. Retroviruses have an envelope and an icosahedral core containing two identical molecules of plus-single-stranded RNA.

The infectious process begins with viral penetration into the cell, occurring in accordance with scheme 1 (see Fig. 5.2), but subsequently proceeds according to scheme 2. Following the release of RNA into the cytoplasm

of the host cell, the RNA-dependent DNA polymerase encoded by the viral genome synthesizes DNA minus-strands on the RNA plus-strands. Then, the RNA strand in the RNA/DNA hybrid is degraded, and a DNA plus-strand is formed on the DNA minus-strand as a template. The resulting double-stranded DNA migrates into the Nucleus of the host cell and integrates into the cellular DNA there.

Retrovirus replication occurs during normal METABOLISM/31.html">Transcription by the cell of its own cellular DNA, into which the viral genome is now integrated. Concurrently, viral proteins are synthesized; together with RNA copies produced by the host cell's transcription enzymes, they form new virions, which then bud through The Plasma Membrane. Frequently, retroviral infection alters the pattern of cell growth, causing cells to behave more like tumor cells than normal cells: their growth becomes rapid and much less dependent on external stimulants such as Hormones or growth factors. It is now known that certain retroviral genes encode proteins capable of maintaining cells in a state of more or less continuous division (Ch. 29). The isolation and identification of these proteins will help elucidate The Mechanism of tumor growth.