T

Transcription j"

I Replication y 5' Input virion RNA(-)

I Replication

Replication

| Replication

Fig. 29-2 Genome structure of vesicular stomatitis virus and its mode of replication Wide bars indicate genes and their relative sizes; narrow bars indicate noncoding nucleotide sequences; the long narrow bar indicates {+) strand complementary RNA The N protein-RNA core plus the NS and L proteins comprise the transcription complex Polyadenylation, signaled by the conserved sequence AljACUUUUUUU at the end of each gene, occurs by a "stuttering" mechanism. RNA replication occurs through a replicative intermediate (•+/-) dsRNA le, leader, N, nucleoprotein; P (NS), nonstructural protein; M, matrix protein; G, peplomer glycoprotein, L, with P, comprises RNA polymerase.

Viral Replication

Laboratory-adapted ("fixed") and wild-type ("street") rabies virus, and vesicular stomatitis virus, replicate to high titer in the brains of suckling mice and in many kinds of cell cultures. Most of our-knowledge of rhabdovirus replication comes from studies of vesicular stomatitis virus (Fig. 29-2).

Virions bind to receptors via glycoprotein G, enter the cell by endocytosis, and are uncoated, releasing the nucleocapsid into the cytoplasm where all subsequent events occur. Primary transcription by the viral transcriptase complex (L + P) produces five monocistronic mRNA species in the order N, P (NS), M, G, and L. Each of these is 5' capped and 3' polyadenylated by the multifunctional enzyme encoded by the L protein. Because there is only a single promoter it is postulated that polyadenylation occurs via polymerase slippage at each intergenic stretch of seven U residues and that, with an efficiency of less than 100%, the transcriptase complex then moves on to the next open reading frame. This is consistent with the observation that the five genes are transcribed in decreasing molar abundance from N at the 3' end through to L at the 5' end of the genome. Transition to the replication mode requires synthesis of a protein, thought to be N protein, which somehow enables the polymerase to read through all the intergenic transcription termination, polyadenylation, and capping signals to produce a full-length authentic complementary copy of genomic RNA. Both plus and minus strands associate with nucleoprotein, but only minus strands associate with M and trigger budding from those areas of plasma membrane that contain glycoprotein G.

Replication of vesicular stomatitis virus usually causes rapid cytopathol-ogy (thought to be attributable to inhibition of cellular mRNA transcription by protein M), but the replication of rabies virus is usually noncytopathic. Defective interfering (DI) virus particles are commonly formed during rhabdovirus replication. These are shorter and have a smaller RNA molecule than normal infectious particles, with complex deletion mutations in their genome (see Chapter 4).

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Stuttering Simple Techniques to Help Control Your Stutter

Stuttering Simple Techniques to Help Control Your Stutter

Discover Simple Techniques to Help Control Your Stutter. Stuttering is annoying and embarrassing. If you or a member of your family stutters, you already know the impact it can have on your everyday life. Stuttering interferes with communication, and can make social situations very difficult. It can even be harmful to your school or business life.

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