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18 The Viruses: Viruses of Eucaryotes

 

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 discussed. The chapter concludes with a discussion of infectious agents that are even simpler than viruses, the viroids and prions.

 

CHAPTER OBJECTIVES

After reading this chapter you should be able to:

! compare and contrast viruses that infect eucaryotes with those that infect procaryotes

! describe the various ways that viruses of eucaryotes can harm their host organisms

! discuss the establishment of chronic or slow virus infections

! discuss the mechanisms that have been proposed for virus involvement in the establishment of certain cancers

! discuss the importance of plant viruses and the technical difficulties that have hindered rapid progress in this area

! discuss fungal and algal viruses

! discuss the potential use of insect viruses for pest control

! discuss the nature and significance of viroids and prions

 

CHAPTER OUTLINE

I. Classification of Animal VirusesCthe most important criteria are virus morphology, nucleic acid properties, and genetic relatedness

A. MorphologyCsize, shape, and presence or absence of envelope

B. Nucleic acid properties

1. DNA or RNA

2. Single stranded or double stranded (ss or ds)

3. Size and/or segmentation

C. Genetic relatednessCnucleic acid hybridization and sequencing

II. Reproduction of Animal Viruses

A. Adsorption of virions

1. Attach to specific receptor sites; usually cell surface glycoproteins that are required by the cell for normal cell functioning

2. May be species-specific or tissue-specific, or may have a broad multispecies host range

3. Many viral receptors are part of the immunoglobulin superfamily

4. Viral surface glycoproteins and/or enzymes may mediate virus attachment to the cellular receptor molecules

B. Penetration and uncoating vary with different viruses

1. Injection similar to that of bacteriophages may be used by some viruses

2. Envelope fusion with the cytoplasmic membrane with resultant deposition of the nucleocapsid core within the cell is used by other viruses

3. Engulfment within coated vesicles (endocytosis) may occur with most viruses; lysosomal enzymes and low endosomal pH often trigger the uncoating process

C. Replication and transcription in DNA viruses

1. Host synthesis of DNA, RNA, and protein may be halted, unaffected, or even stimulated

2. Viral DNA replication usually occurs in the nucleus; however, in poxviruses it occurs in the cytoplasm

3. Transcription usually uses host RNA polymerase (poxviruses are an exception)

4. Gene expression may be divided into early and late phases

5. Some viruses use overlapping genes to package more information into a very small genome

D. Replication and transcription in RNA viruses

1. RNA viruses are more diverse in their reproductive strategies than are DNA viruses

2. Plus-strand viruses use genome RNA as mRNA

3. Minus-strand viruses produce replicative form (dsRNA), using a virion-associated transcriptase, and then produce mRNA

4. Double-stranded RNA viruses use a virion-associated transcriptase for replication and mRNA production

5. Retroviruses make a dsDNA copy (called proviral DNA) using the enzyme reverse transcriptase

a. The proviral DNA is integrated into the host chromosome

b. The integrated proviral DNA can then direct the synthesis of mRNA

c. Sometimes these viruses can change the host cells into tumor cells

E. Synthesis and assembly of virus capsids

1. Capsid proteins are synthesized by host cell ribosomes under the direction of the late genes

2. Empty procapsids are produced

3. Nucleic acid is inserted

4. Enveloped virus nucleocapsids are assembled similarly, except for poxvirus nucleocapsids

F. Virion release

1. Naked viruses are released when host cell lyses

2. Enveloped viruses are usually released by the following mechanisms:

a. Virus-encoded proteins are incorporated into plasma membrane

b. Nucleocapsid buds outward, forming the envelope during release

3. Herpesvirus envelope formation usually involves the host=s nuclear envelope rather than the plasma membrane; other membrane structures can also be used by certain viruses

4. Poxviruses use actin cytoskeleton microfilaments to propel them through the plasma membrane and thereby escape without destroying the host cell

III. Cytocidal Infections and Cell DamageCdamage may or may not result in cell death; if death occurs the infection is cytocidal; mechanisms of host cell damage may include:

A. Inhibition of host DNA, RNA, and protein synthesis

B. Lysosome damage, leading to release of hydrolytic enzymes into the cell

C. Plasma membrane alteration leading to host immune system attack on the cell or to cell fusion

D. Toxicity from high protein concentrations

E. Formation of inclusion bodies that may cause direct physical disruption of cell structure

F. Chromosomal disruptions

G. Malignant transformation to a tumor cell

IV. Persistent, Latent, and Slow Virus Infections

A. In persistent (chronic) infections, the virus reproduces at a slow rate without causing disease symptoms

B. In latent infections, the virus stops reproducing and remains dormant for a period before becoming active again

C. Slow virus infections are those that cause progressive, degenerative diseases with symptoms that increase slowly over a period of years

D. Defective interfering (DI) particles are usually produced by deletion mutations; they cannot reproduce but they slow normal virus reproduction, thereby reducing host damage and establishing a chronic infection

V. Viruses and Cancer

A. Viruses may cause cancer by a variety of mechanisms

1. Virus may carry one or more cancer-causing genes (oncogenes)

2. 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

3. Viruses may produce a regulatory protein, which in turn activates a cellular oncogene

B. Viruses and Human Cancers

1. Epstein-Barr virus (EBV)Ca herpesvirus that may cause:

a. Burkitt=s lymphoma; found mostly in central and western Africa

b. Nasopharyngeal carcinoma; found in southeast Asia

c. Infectious mononucleosis; found in the rest of the world

d. Evidence suggests that host infection with malaria is necessary for EBV to cause Burkitt=s lymphoma; this is supported by the low incidence of Burkitt=s 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

C. Viral etiology of human cancers is difficult to establish because Koch=s postulates could only be satisfied by experimenting on humans

VI. Plant Viruses

A. Virion morphology does not differ significantly from that of animal viruses or bacteriophages

B. Plant virus taxonomyCalmost all are RNA viruses and are classified on the basis of nucleic acid type, strandedness, capsid symmetry, size, and the presence or absence of an envelope

C. Plant virus reproduction (using tobacco mosaic virus as an example)

1. The virus uses either a cellular or a virus-specific RNA replicase; the evidence is not clear

2. The virus produces proteins, which then spontaneously assemble

3. The virus causes many cytological changes, such as the formation of inclusion bodies and the degeneration of chloroplasts

4. Viral spread is through the plant vascular system

D. Transmission of plant viruses is sometimes difficult because of 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

VII. Viruses of Fungi and Algae

A. Fungal viruses

1. Higher fungi are infected by dsRNA viruses that are most often latent rather than cytopathic viruses

2. Lower fungi are infected by dsRNA or dsDNA viruses that cause lysis of infected cells

B. Algal viruses have been detected in electron micrographs, but have not been well studied

VIII. Insect Viruses

A. Members of at least seven virus families are known to infect insects

B. Infection is often accompanied by formation of granular or polyhedral inclusion bodies

C. May persist as latent infections

D. Current interest in most insect viruses focuses on their use as a possible means of 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

IX. Viroids and Prions

A. 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

B. Prions

1. Proteinaceous infectious particles

2. No apparent nucleic acid, only a protein called PrP has been identified

3. Genetic activity is unknown, but the existence of a small, untranslated nucleic acid that interacts with the host cell has not been ruled out; such an infectious agent containing this small nucleic acid coated by PrP would be called a virino

4. Cause progressive, degenerative central nervous system disorders

a. Scrapie in sheep and goats

b. Bovine spongiform encephalopathy (mad cow disease)

c. Kuru (found only in the Fore, an eastern New Guinea tribe that practice ritual cannibalism)

d. Creutzfeldt-Jakob, fatal familial insomnia and Gerstmann-Strassler-Scheinker Syndrome are all human diseases caused by prions

5. Mechanism of pathogenesis may involve a conformational change in the PrP to an abnormal form


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