BTY328: Viruses Dr William Stafford Viral hosts and disease Viruses that infect eukaryotes: plants and animals

Diversity of viruses that infect vertebrates Microbiologists first began to classify animal viruses in terms of host preferences. However, many viruses will infect a variety of animals, and a particular animal can be invaded by several dissimilar viruses.... Modern classifications are primarily based on virus morphology, the physical and chemical nature of virion constituents, and genetic relatedness.

Reproduction of human phages adsorption, penetration and uncoating, replcation of virus nucleic acids, synthesis and assembly of virus capsids, and release of mature viruses. The reproduction of animal viruses is very similar in many ways to that of phages: stages: adsorption, penetration and uncoating, replcation of virus nucleic acids, synthesis and assembly of virus capsids, and release of mature viruses. receptors Host and tissue specificity The capacity of a virus to infect a cell depends on its ability to bind target receptors. Host and tissue specificity e.g poliovirus receptors are found only in the human nasopharynx, gut, and spinal cord; whereas, measles virus receptors are present in most tissues.

Viral entry Some naked viruses such as the poliovirus undergo major change in capsid structure on adsorption to the plasma membrane, and only their nucleic acids are injected into the cytoplasm. Many enveloped viruses enter cells through engulfment by receptor-mediated endocytosis to form coated vesicles. These vesicles fuse with lysosomes where viral uncoating is completed. The envelope of paramyxoviruses, membrane fusion occurs- membrane lipids rearrange and adjacent membranes merge, and a proteinaceous fusion pore forms. Then nucleocapsid enters the host cell cytoplasmic matrix, where uncoating is completed.

Strategies of viral entry

Viral genome replication strategies

Replication and Transcription in DNA Viruses The early phase of infection aims to take over the host cell and to the synthesise viral DNA and RNA. Some virulent animal viruses inhibit host cell DNA, RNA, and protein synthesis, although cellular DNA is not usually degraded. Parvoviruses (canine and feline leukopenia)- small, ssDNA molecule about 4.8kbp with overlapping genes; directs the synthesis of only three capsid polypeptides. Since the genome does not code for any enzymes, the virus must use host cell enzymes for all biosynthetic processes (viral DNA can only be replicated in the nucleus during the S-phase of the cell cycle, when the cell replicates its own DNA).

Replication and Transcription of DNA Viruses Herpesviruses- icosahedral, enveloped, dsDNA viruse with a genome of 160 kbp coding for genes. Immediately upon infection, the DNA is transcribed by host RNA polymerase to form mRNAs directing the synthesis of viral proteins. Poxviruses such as the vaccinia virus are dsDNA and the largest viruses known, the genome is 190kbp coding for 250 genes. The viral core contains both DNA and RNA polymerases that synthesize early mRNAs, which then produce viral proteins. The complete reproductive cycle in poxviruses about 24 hours.

Replication and Transcription of RNA Viruses ssRNA viruses, except retroviruses, use a viral replicase that converts the ssRNA into adouble-stranded RNA called the replicative form that then directs the synthesis of new viral RNA genomes Picornaviruses (e.g poliovirus) (+) strand ssRNA. Use their RNA genome as a large mRNA, that results in the synthesis of an enormous polypeptide that is processed. Orthomyxoviruses (e.g Influenza) (-) strand ssRNA. Use a viral RNA-dependent RNA polymerase to synthesize mRNA and subsequently proteins. Retroviruses (e.g.HIV) (+) strand ssRNA but differ from other RNA viruses that replicate their genome by means of DNA intermediates. The virus has an RNA-dependent DNA polymerase or reverse transcriptase.

Replication and Transcription of RNA Viruses dsRNA viruses use a RNA-dependent RNA polymerase that copies the negative strand of their genome to generate mRNA. Normally use a single polymerase for replication and transcription. Reoviruses use a different strategy. The virion contains 10 to 13 different dsRNAs, each coding for an mRNA. Late in the re­productive cycle, these mRNA associates and are copied by the viral replicase to form a double-stranded genome that is incorporated into a new virion.

Viral release Mechanisms of virion release is different for naked and enveloped viruses. Naked virions appear to be released most often by host cell lysis, causing cell death. In contrast, the release of enveloped viruses is usually by membrane budding and the host cell may continue to release virions for some time. Host actin filaments can also aid in virion release (e.g. vaccinia virus) by moving virus in the cytoplasm and propelling it through the plasma membrane without destroying the cell.

Summary: Influenza virus Life cycle of Influenza virus

Influenza virus release

Viruses that infect Plants

Tobacco Mosaic Virus (TMV)‏ TMV is a (+) ssRNA virus that uses complex replication strategy involving intermediates. After the coat protein and RNA genome have been synthesized, they spontaneously assemble into complete TMV virions in a highly organized process Central RNA core with protein protomers arranged in a helical spiral.

TMV infection and reproduction TMV-infected cells produce microscopically visible intracellular inclusions, usually composed of virion aggregates. The host cell chloroplasts become abnormal and often degenerate and new chloroplast synthesis is inhibited. Leaves may appear chlorotic. Reproduction within the host depends on the virus's ability to spread throughout the plant. Viruses can move long distances through the plant vasculature (usually phloem). The spread in nonvascular tissue is hindered by the presence of tough cell walls. TMV does spread slowly from cell to cell through the plasmodesmata

Transmission of Plant Viruses Since plant cells are protected by cell walls, plant viruses have a considerable obstacle to overcome when trying to establish themselves in a host. TMV and a few other viruses may be carried by the wind or animals and then enter when leaves are mechanically damaged. The most important agents of transmission (vectors) are insects that feed on plants, particularly sucking insects such as aphids and leafhoppers. Other vectors such as soil nematodes can transmit viruses (e.g., the tobacco ringspot virus) while feeding on roots.

Acute and persistent infections Many virus infections (e.g. influenza) are acute infection- fairly rapid onset and last for a relatively short time. However, some viruses can establish persistent infections lasting many years. Persistent infections are: chronic - virus is almost always de­tectable and clinical symptoms may be either mild or absent for long periods (e.g hepatitis B and HIV). latent- virus stops reproducing and remains dormant for a period before becoming active again. During latency, no symptoms, antibodies, or viruses are detectable. (e.g. herpes simplex virus, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus.)‏

Effects of viral infection