THE VIRUSES: VIRUSES OF EUCARYOTES

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Chapter Overview

This chapter focuses on the characteristics of viruses that infect eucaryotes. Animal (mammalian) viruses are emphasized because they are causative agents of many human diseases. Other viruses, such as plant viruses and insect viruses, are also mengetahuied. The chapter concludes with a mengetahuiion of infectious agents that are even simpler than viruses, the viroids and prions.

Chapter Objectives

After reading this chapter you should be able to:

1. compare and contrast viruses that infect eucaryotes with those that infect procaryotes
2. describe the various ways that viruses of eucaryotes can harm their host organisms
3. discuss the establishment of persistent virus infections
4. discuss the mechanisms by which viruses may contribute to the development of certain cancers
5. discuss the importance of plant viruses and the technical difficulties that have hindered rapid progress in understanding them
6. discuss fungal and algal viruses
7. discuss the potential use of insect viruses for pest control
8. discuss the nature and significance of viroids and prions

These are the most important concepts you are learning in this chapter:

1.       Although the details differ, animal virus reproduction is similar to that of the bacteriophages in having the same series of phases: adsorption, penetration and uncoating, replication of virus nucleic acids, synthesis and assembly of capsids, and virus release.

2.       Viruses may harm their host cells in a variety of ways, ranging from direct inhibition of DNA, RNA, and protein synthesis to the alteration of plasma membranes and formation of inclusion bodies.

3.       Not all animal virus infections have a rapid onset and relatively short duration. Some viruses establish long-term chronic infections; others are dormant for a while and then become active again. Slow virus infections may take years to develop.

4.       Cancer can be caused by a number of factors, including viruses. Viruses may bring oncogenes into a cell, carry promoters that stimulate a cellular oncogene, or in other ways transform cells into tumor cells.

5.       Plant viruses are responsible for many important diseases but have not been intensely studied due to technical difficulties. Most are RNA viruses. Insects are the most important transmission agents, and some plant viruses can even multiply in insect tissues before being inoculated into another plant.

6.       Members of at least seven virus families infect insects; the most important belonging to the Baculoviridae Reoviridae, or Iridoviridae. Many insect infections are accompanied by the formation of characteristic inclusion bodies. A number of these viruses show promise as biological control agents for insect pests.

Study Outline

1. Classification of Animal Viruses
1. Morphology-most important characteristic for classification
2. Physical and chemical nature of virion, especially nucleic acids, are also important for classification
3. Genetic relatedness-can be estimated by nucleic acid hybridization and sequencing
2. Reproduction of Animal Viruses
1. Adsorption of virions
1. Attach to specific receptor sites; usually cell surface glycoproteins that are required by the cell for normal cell functioning (e.g., hormone receptors, chemokine receptors)
2. Viral surface glycoproteins and/or enzymes may mediate virus attachment to the cellular receptor molecules
2. Penetration and uncoating
1. Little is known about precise mechanisms, but there appear to be three different modes of entry
1. Changes in capsid structure leads to entry of nucleic acid into host
2. Fusion of viral envelope with the host cytoplasmic membrane results in deposition of the nucleocapsid core within the cell
3. Engulfment of virus within coated vesicles (endocytosis); lysosomal enzymes and low endosomal pH often trigger the uncoating process
2. Once in the cytoplasm the nucleic acid may function while still attached to capsid components or may only after completion of uncoating
3. Replication and transcription in DNA viruses
1. Expression of early viral genes (usually catalyzed by host enzymes) is devoted to taking over host cell; this may involve halting synthesis of host DNA, RNA, and protein or in some cases these processes may be stimulated
2. Later, viral DNA replication occurs, usually in the nucleus
3. Some examples
1. Parvoviruses (ssDNA)-have a very small genome with overlapping genes; use host enzymes for all biosynthetic process
2. Herpesviruses (dsDNA)-host RNA polymerase is used to transcribe early genes; DNA replication is catalyzed by viral DNA polymerase
3. Poxviruses (dsDNA)-viral RNA polymerase synthesizes early mRNA; one of the early gene products is viral DNA polymerase, which replicates the viral genome
4. Hepadnaviruses (circular dsDNA)-use reverse transcriptase to replicate its DNA genome via an RNA intermediate
4. Replication and transcription in RNA viruses
1. Transcription in RNA viruses (except retroviruses)
1. +strand RNA viruses use their genome as mRNA
2. -strand RNA viruses use viral RNA-dependent RNA polymerase (transcriptase) to synthesize mRNA, using the genome as the template
3. dsRNA viruses use viral RNA-dependent RNA polymerase to synthesize mRNA
2. Replication in RNA viruses (except retroviruses)
1. ssRNA viruses use viral replicase (an RNA-dependent RNA polymerase) to convert ssRNA into dsRNA (replicative form); replicative form serves as template for genome synthesis
2. dsRNA viruses-viral mRNA molecules associate with special proteins to form a large complex; replicase then uses these mRNA molecules as templates for synthesis of dsRNA genome
3. For dsRNA viruses and -strand RNA viruses, the viral RNA-dependent RNA polymerase functions both as the transcriptase and the replicase; the mode of action depends on associated proteins and other factors
4. Retroviruses make a dsDNA copy (called proviral DNA) using the enzyme reverse transcriptase
1. The proviral DNA is integrated into the host chromosome
2. The integrated proviral DNA can then direct the synthesis of mRNA
3. Sometimes these viruses can change the host cells into tumor cells
5. Synthesis and assembly of virus capsids
1. Capsid proteins are synthesized by host cell ribosomes under the direction of viral late genes
2. Empty procapsids are produced
3. Nucleic acid is inserted
4. Enveloped virus nucleocapsids are assembled similarly (except for poxvirus nucleocapsids, which are assembled by a complex process that begins with enclosure of some of the cytoplasmic matrix by construction of a membrane, followed by movement of viral DNA into the center of the immature virus)
6. Virion release
1. Naked viruses are usually released when host cell lyses
2. Enveloped viruses are usually released by the following mechanisms:
1. Virus-encoded proteins are incorporated into plasma membrane (some viruses use nuclear membrane, endoplasmic reticulum, Golgi apparatus, or other membranes)
2. Nucleocapsid buds outward, forming the envelope during release
3. Actin cytoskeleton microfilaments can aid virion release (e.g., poxviruses) without destroying the host cell
3. Cytocidal Infections and Cell Damage
1. Viruses often damage their host cells, in some cases causing cell death; if death occurs the infection is cytocidal
2. Seven mechanisms for causing cell damage have been identified
1. Inhibition of host DNA, RNA, and protein synthesis
2. Lysosome damage, leading to release of hydrolytic enzymes into the cell
3. Plasma membrane alteration, leading to host immune system attack on the cell or to cell fusion
4. Toxicity from high viral protein concentrations
5. Formation of inclusion bodies that may cause direct physical disruption of cell structure
6. Chromosomal disruptions
7. Malignant transformation to a tumor cell
4. Persistent, Latent, and Slow Virus Infections
1. Persistent infections-long lasting infections
1. Chronic infection-virus is usually detectable, but clinical symptoms are mild or absent for long periods
2. Latent infections-virus stops reproducing and remains dormant for a period before becoming active again; during latency, no symptoms, antibodies or viruses are detectable
2. Causes of persistence and latency are probably multiple
1. Viral genome integrates into host chromosome
2. Virus becomes less antigenic
3. Virus mutates to less virulent and slower reproducing form
4. Deletion mutation produces defective interfering (DI) particles, which cannot reproduce but slow normal virus reproduction and thereby reduce host damage and establish a chronic infection
3. Slow virus infections are those that cause progressive, degenerative diseases with symptoms that increase slowly over a period of years
5. Viruses and Cancer
1. Cancer-a disease where there is abnormal cell growth (neoplasia) and the spread of the abnormal cells throughout the body (metastasis)
1. Tumor-a growth or lump of tissue; can be benign (nonspreading) or malignant (cancerous)
2. Carcinogenesis is a complex, multistep process that involves a triggering event and the activity of oncogenes
2. Viral etiology of human cancers is difficult to establish because Kochís postulates can only be satisfied for these diseases by experimenting on humans
3. Viruses and human cancers
1. Epstein-Barr virus (EBV)-a herpesvirus that may cause:
1. Burkittís lymphoma; found mostly in central and western Africa
2. Nasopharyngeal carcinoma; found in Southeast Asia
3. Infectious mononucleosis; found in the rest of the world
4. Evidence suggests that host infection with malaria is necessary for EBV to cause Burkittís lymphoma; this is supported by the low incidence of Burkittís lymphoma in the U.S. where there is almost no malaria
2. Hepatitis B virus may be associated with one form of liver cancer
3. Human papillomavirus has been linked to cervical cancer
4. Human T-cell lymphotropic viruses (the retroviruses HTLV-1 and HTLV-2) are associated with adult T-cell leukemia and hairy-cell leukemia, respectively
4. Viruses may cause cancer by a variety of mechanisms
1. Virus may carry one or more cancer-causing genes (oncogenes)
2. Viruses may produce a regulatory protein, which activates cell division
3. Viruses may insert a promoter or enhancer next to a cellular oncogene (an unexpressed cellular gene that regulates cell growth and reproduction), causing an abnormal expression of this gene and thereby deregulating cell growth
6. Plant Viruses
1. Have not been well studied, primarily because they are difficult to cultivate and purify
2. Virion morphology does not differ significantly from that of animal viruses or bacteriophages; most are RNA viruses
3. Plant virus taxonomy-classified on the basis of nucleic acid type, strandedness, capsid symmetry, size, and the presence or absence of an envelope
4. Plant virus reproduction (using tobacco mosaic virus as an example)
1. The virus uses either a cellular or a virus-specific RNA-dependent RNA polymerase
2. The virus produces proteins, which then spontaneously assemble
3. Viral spread is through the plant vascular system
4. The virus causes many cytological changes, such as the formation of inclusion bodies and the degeneration of chloroplasts
5. Transmission of plant viruses-process is complicated by the tough walls that cover plant cells
1. Some may enter only cells that have been mechanically damaged
2. Some are transmitted through contaminated seeds, tubers, or pollen
3. Soil nematodes can transmit viruses while feeding on roots
4. Some may be transmitted by parasitic fungi
5. Most important agents of transmission are insects such as aphids or leafhoppers that feed on plants
7. Viruses of Fungi and Algae
1. Most viruses of higher fungi (mycoviruses) are dsRNA viruses that cause latent infections
2. Viruses of lower fungi are dsRNA or dsDNA viruses that cause lysis of infected cells
3. Algal viruses have been detected in electron micrographs, but have not been well studied
8. Insect Viruses
1. Members of at least seven virus families are known to infect insects
2. Infection is often accompanied by formation of granular or polyhedral inclusion bodies
3. May persist as latent infections
4. Current interest in most insect viruses focuses on their use for biological pest control; they have several advantages over chemical toxins:
1. They are invertebrate-specific and, therefore, should be safe
2. They have a long shelf life and high environmental stability
3. They are well suited for commercial production because they reach high concentrations in infected insects
9. Viroids and Prions
1. Viroids
1. Circular ssRNA molecules
2. No capsids
3. Cause diseases in plants
4. Do not act as mRNAs
5. Mechanism that produces symptoms of disease is unknown
6. May give rise to latent infections
2. Prions
1. Proteinaceous infectious particles (PrP) that are not associated with a nucleic acid
2. Genes have been identified in normal animal tissue that encode PrP

It is hypothesized that abnormal PrP causes prion diseases by inducing a change from the normal conformation of the cellular PrP to the abnormal form b. This new abnormal PrP then causes other normal cellular PrP molecules to change to the abnormal form

3. Cause progressive, degenerative central nervous system disorders
1. Scrapie in sheep and goats
2. Bovine spongiform encephalopathy (mad cow disease)
3. Kuru (found only in the Fore, an eastern New Guinea tribe that practice ritual cannibalism)
4. Creutzfeldt-Jakob, fatal familial insomnia and Gerstmann-Strassler-Scheinker Syndrome are all human diseases caused by prions

Chapter Web Links

Common Cold web site (http://www.commoncold.org/)

All the Virology on the WWW (http://www.tulane.edu/~dmsander/garryfavweb.html)

The Big Picture Book of Viruses (http://www.tulane.edu/~dmsander/Big_Virology/BVHomePage.html)

Electron microsopic images of Human Viruses (http://www.uct.ac.za/depts/mmi/stannard/linda.html) Linda Stannard's "illustrated tutorial on the morphology of most of the clinically significant viruses".

Visualizations of Viruses at the University of Wisconsin - Madison (http://www.bocklabs.wisc.edu/virusviztop.html)