1. Viruses, Viroids, and Prions
Chapter 13
Viruses, Viroids, and Prions

2. Viruses Viroids Prions an ultramicroscopic - 20 to 300 nm in diameter
replicates only within the cells of living hosts (bacteria, plants, and animals)
composed of an RNA or DNA core, a protein coat, and, in more complex types, a surrounding envelope.
Viroids
consists solely of a strand of RNA
smaller than a virus
an infectious particle - capable of causing disease
Prions
an infectious protein particle similar to a virus but lacking nucleic acid;

3. Viruses Acellular Viral size is ascertained by electron microscopy
Consist of DNA or RNA core
Core is surrounded by a protein coat
Coat may be enclosed in a lipid envelope
Reproduction – use host resources
Viruses are replicated only when they are in a living host cell
Obligate cellular parasite
Figure 1.1e

4. Virus structure Virion - a fully assembled infectious virus
1. Core- Nucleic acid – viral genome
Single- or double-stranded RNA or DNA
Encodes for only a few structural proteins (Capsid proteins )
Non-structural regulatory proteins involved in virus replication
2. Protein coat - capsid
Single or double protein shells
Consist of only one or a few structural protein species
Capsomer - The single protein unit
Multiple protein copies must self assemble to form the continuous three-dimensional capsid structure.
Shell Function
Protect the viral genome from nucleases.
Attaches the virion to specific receptors exposed on the prospective host cell during infection.

5. Virus structure 3. Envelope
Some virus families have an additional lipid bilayer cover closely surrounding the shell of the virus
It is usually derived in part from modified host cell membranes.
Virus-encoded membrane-associated proteins
The exterior of the bilayer is studded with virus-coded glycosylated trans- membrane proteins (glycoproteins)
Spikes or knobs, also called peplomers.

6. Virus structure Helical viruses
The protein subunits and the nucleic acid are arranged in a helix.
Polyhedral viruses
The protein subunits assemble into a symmetric shell that covers the nucleic acid-containing core.
Complex Viruses
Often have architecture consisting of both helical and polyhedral parts confined to different structural components

7. Viruses reproduction
The main function of the virion is to deliver its DNA or RNA genome into the host cell so that the genome can be expressed (transcribed and translated) by the host cell.
For propagation viruses depend on specialized host cells supplying the complex metabolic and biosynthetic machinery of eukaryotic or prokaryotic cells.
Host range is determined by specific host attachment sites and cellular factors
Most viruses infect only one host
Viruses may be viewed as mobile genetic elements, most probably of cellular origin and characterized by a long co-evolution of virus and host.

8. Viral Taxonomy Family names end in -viridae Genus names end in -virus
Viral species: A group of viruses sharing the same genetic information (DNA or RNA) and ecological niche (host).
Common names are used for species
Subspecies are designated by a number
Example:
Herpesviridae
Herpesvirus
Human herpes virus HHV-1, HHV-2, HHV-3
Retroviridae
Lentivirus
Human immunodeficiency virus HIV-1, HIV-2

9. The most important taxonomic criteria
Genome Type
Particle Morphology – symmetry and viral core structure, envelope.
Host organism(s) - Hosts of viruses include all classes of cellular organisms described to date.

10. Genomic diversity among viruses
Nucleic acid
DNA
RNA (RNA viruses, comprising 70% of all viruses, vary remarkably in genome structure.)
Because of the error rate of the enzymes involved in RNA replication, these viruses usually show much higher mutation rates than do the DNA viruses.
Mutation rates of 10-4 lead to the continuous generation of virus variants which show great adaptability to new hosts
Both DNA and RNA (at different stages in the life cycle)
Shape
Linear (adenoviruses )
Circular (polyomaviruses )
Segmented (some RNA viruses )
Strandedness
Single-stranded
Double-stranded
Double-stranded with regions of single-strandedness (Hepadnaviridae)
Sense
Positive sense (+)
Negative sense (antisense)
Ambisense (+/−)

11. Schemes of 21 virus families infecting humans showing a number of distinctive criteria:
an envelope or (double-) capsid
nucleic acid genome:
+, Sense strand;
-, antisense strand;
±, dsRNA or DNA;
0, circular DNA;
C, number of capsomers, where known;
nm, dimensions of capsid, or envelope when present;

12. Multiplication of Bacteriophages
Bacteriophage – bacterial viruses – complex viruses
Lytic cycle Phage causes lysis and death of host cell
Lysogenic cycle Prophage DNA incorporated in host DNA

13. Multiplication of Bacteriophages (Lytic cycle)
1. Attachment
2. Penetration
3. Biosynthesis
4. Maturation
5. Release

14. Multiplication of Bacteriophages (Lysogenic Cycle)
Figure 13.12

15. Generalized Transduction Specialized Transduction2 3 4 5 6
Figure 8.28

16. Multiplication of Animal viruses
Attachment Penetration Uncoating
# by endocytosis by viral or host enzymes
# by fusion
Figure 13.14a

17. Multiplication of Animal viruses
4. Biosynthesis - Production of nucleic acid and proteins (In nucleus (DNA viruses) or cytoplasm (RNA viruses)
5. Maturation - Nucleic acid and capsid proteins assemble
6. Release
- By rupture
- By budding (enveloped viruses)

18. Multiplication of DNA-Containing Virus
1.Viral DNA is replicated in the
host nucleus
2.Viral proteins are made in the cytoplasm
3. Viral assemble into virions in the nucleus
4. The virions are then transported
through the host ER for release
*Viral DNA is usually, but not always, integrated into the cell chromosomes at random sites. Only part of the viral genome is expressed
*The family of Papovaviridae is not longer used in recent taxonomy, but is split into the Papillomaviridae and the Polyomaviridae.

19. Multiplication of RNA-Containing Viruses
Both the viral RNA and proteins are synthesized in the cytoplasm
RNA dependent RNA polymerase
-Virions assemble in the cytoplasm
Figure 13.17

20. Multiplication of Retroviruses
RNA +strand
Reverse transcription
Synthesis of dsDNA
Transport to the nuclei
Integrates in the host
genome –Provirus DNA
The provirus can then remain latent
Transcription activation
Genome, or the genes can be expressed to create virions
Assembly
Release
Figure Overview

21. Virus Families That Affect Humans
Single-stranded DNA, nonenveloped viruses
Parvoviridae - Anemia in immunocompromised patients
Double-stranded DNA, nonenveloped viruses
Adenoviridae - Respiratory infections in humans, tumors in animals
Papovaviridae
Papillomavirus - Human wart virus
Polyomavirus - Cause tumors; some cause cancer
- Double-stranded DNA, enveloped viruses
Poxviridae
Orthopoxvirus (vaccinia and smallpox viruses)
Herpesviridae
Simplexvirus (HHV-1 and HHV-2)
Varicellovirus (HHV-3)
Lymphocryptovirus (HHV-4)
Cytomegalovirus (HHV-5)
Roseolovirus (HHV-6)
HHV-7
Kaposi's sarcoma (HHV-8)
Some herpesviruses can remain latent in host cells
Hepadnaviridae Hepatitis B virus
DNA single strand
Blood borne pathogen

22. Virus Families That Affect Humans
Single-stranded RNA, + strand, nonenveloped
Picornaviridae - enterovirus
Hepatitis A virus
Single-stranded RNA, + strand, enveloped
Togaviridae
Rubivirus (rubella virus)
Flaviviridae
West Nile viruses,
Hepatitis C virus
Single-stranded RNA, – strand, one RNA strand
Rhabdoviridae
Lyssavirus (rabies virus)
Filoviridae
Ebola and Marburg viruses
Paramyxoviridae
Morbilli virus, Parainfluenza,Mumps
Single-stranded RNA, – strand, multiple RNA strands
Orthomyxoviridae - Envelope spikes can agglutinate RBCs
Influenzavirus (influenza viruses A and B)
Influenza C virus

23. Avian Influenza
(Lectin)
Clinical Focus, p. 371

24. Virus Families That Affect Humans
Single stranded RNA, 2 RNA strands, produce DNA
Retroviridae
Use reverse transcriptase to produce DNA from viral genome
Lentivirus (HIV)
Oncogenic viruses
Includes all RNA tumor viruses

25. Cancer
Tumor is a general term used to describe the uncontrollable growth of cells.
Tumors can be Benign
Malignant (cancerous)
An oncogene is a gene that, when mutated or expressed at high levels, helps turn a normal cell into a cancer cell
Activated oncogenes transform normal cells into cancerous cells:
increased growth
loss of contact inhibition
tumor specific transplant and T antigens.
A proto-oncogene is a normal gene that can become an oncogene
Proto-oncogenes code for proteins that help to regulate cell growth and differentiation.
The region of the viral genome that can cause a tumor (DNA in DNA tumor-viruses or RNA in RNA-tumor viruses).
This foreign gene can be carried into a cell by the virus and cause the host cell to take on new properties.

26. Oncogenic Viruses Oncogenic DNA Viruses Adenoviridae Herpesviridae
Poxviridae
Papovaviridae
Hepadnaviridae
Oncogenic RNA viruses
Retroviridae
Viral RNA is transcribed to DNA which can integrate into host DNA
Examples:
1. EBV > Nasopharyngeal cancer
2. RNA virus -----> breast cancer
3. Genital Herpes > cervical cancer
4. Genital warts -----> cervical cancer (specifically HPV-16)
5. unknown virus > cervical cancer carried in sperm

27. Viral infection Acute Infection Latent Viral Infections
During an acute infection, the virus essentially hijacks the cellular machinery
Influenza virus infection.
Latent Viral Infections
After infection the viral genome is replicated in conjunction with host DNA;
expression of viral genes is absent or inefficient; the viral genome remains intact
an acute infection may occur at a later time.
Herpes virus - Cold sores, shingles
Persistent Viral Infections
Involve stages of both silent and productive
infection without rapidly killing or even
producing excessive damage of the host cells.
Disease processes occurs over
a long period, generally fatal-
Subacute sclerosing panencephalitis
(measles virus)

28. Growing Viruses - Viruses must be grown in living cells.
Bacteriophages form plaques on
a lawn of bacteria.
Animal viruses may be grown in
living animals or in embryonated eggs.
Animal and plants viruses may be grown in cell culture.
Continuous cell lines may be maintained indefinitely.
Figure 13.6

29. Virus Identification Cytopathic effects Serological tests
Detect antibodies against viruses in a patient
Use antibodies to identify viruses in neutralization tests, viral hemagglutination, and Western blot
Nucleic acids
RFLPs - A Restriction Fragment Length Polymorphism (or RFLP, often pronounced as "rif-lip") is a variation in the DNA sequence of a genome which can be detected by a laboratory technique.
PCR

30. Plant viruses enter through wounds or via insects Viroids
Viroids are infectious peaces of RNA; potato spindle tuber disease
Figure 13.22

31. Prions
Prion (protein-infection) is an infectious agent composed only of protein in a misfolded form.
Inherited and transmissible by ingestion, transplant, & surgical instruments
Spongiform encephalopathies
because of the post mortem appearance of the brain with large vacuoles in the cortex and cerebellum
Sheep scrapie
Creutzfeldt-Jakob disease
Gerstmann-Sträussler-Scheinker syndrome
Fatal familial insomnia
Mad cow disease

32. Prions
Prions propagate by transmitting a misfolded protein state. When a prion enters a healthy organism, it induces existing, properly folded proteins to convert into the disease-associated, prion form; the prion acts as a template to guide the misfolding of more protein into prion form.

33. Learning objectives Differentiate a virus from a bacterium.
Describe the chemical composition and physical structure of an enveloped and a nonenveloped virus.
Define viral species.
Give an example of a family, genus, and common name for a virus.
Describe the lytic cycle of bacteriophages.
Describe the lysogenic cycle of bacteriophage lambda.
Compare and contrast the multiplication cycle of DNA- and RNA-containing animal viruses.
Define oncogene and transformed cell.
Discuss the relationship between DNA- and RNA-containing viruses and cancer.
Differentiate between persistent viral infections and latent viral infections.
Describe how bacteriophages are cultured.
Describe how animal viruses are cultured.
List three techniques that are used to identify viruses.
Discuss how a protein can be infectious.
Differentiate virus, viroid, and prion.