Chapter 13-Viruses. Viroids, and Prions

General Characteristics of all viruses

• Contain a single type of nucleic acid

• Contain a protein coat

• Obligate intracellular parasites

• Are viruses the only known obligate intracellular parasites?

History began with the Tobacco Mosaic Virus (TMV)

• 1886 Aldolf Mayer showed that a virus was transmissable between plants

• 1892 Iwanowski tried to isolate it by filtering with porcelain filter

Sizes of viruses

Common Shapes

• Capsid coat made of capsomeres

• Nucleic acid inside

Two different types of Viruses

Relationship of virus with host cell

Bacterial viruses

• Known as bacteriophages or phages

• Two different life cycles1. Lytic cycle (lytic or virulent phage)-results in

lysis of the cell

2. Lysogenic cycle (temperate or lysogenic phage)-may result in lysis of the cell or becomes a permanent part of the chromosome by integrating

T4 phage replication

Lambda Phage replication

Lambda integrates into the chromosome

Properties conferred by prophage

Some phage are filamentous

Replication of filamentous phage

M13 is ssDNA…how does it replicate the ssDNA?

How do bacteria protect themselves against phage?

• Prevent phage attachment

• Attacking foreign DNA with restriction enzymes, protecting native DNA with methylation

• CRISPR system degrades incoming viral nucleic acid

CRISPR defense system against phage

Methods to study bacteriophage

• Plaque Assay used to quantitate phage

How do animal viruses differ from bacterial viruses?

• Attachment or entry into the cell

• Replication of viral nucleic acid (remember eukaryotic cells have a nucleus)

• Uncoating step is required by animal viruses

• Exit the host cell by budding or shedding

Effects of animal virus on cells

Entry of animal virus

Replication strategies

• Watch the type of nucleic acid

• What enzymes are needed for the process?

Release of enveloped viruses

Acute viral infections

• Usually short in duration

• Host develops long lasting immunity

• Infection of the virus results in a productive infection…host cells die as a result of infection

General Steps of Acute Viral infection

• Attachment• Entry into host cell• Targeting where it will reproduce• Uncoating of the capsid• Synthesis of proteins, replication of nucleic acid• Maturation• Cell lysis

Can you identify some examples of viruses that produce an acute viral infection?

Persistent infections

• Virus is continually present in the body, released by budding

• Three categories– Latent infections– Chronic infections– Slow infections

Persistent: Latent Infections

• Persistent infection with symptomless period followed by reactivation of virus and symptoms

• Example of latent viruses are found in the family Herpesviridae – Herpes simplex virus -1– Herpes simplex virus -2

Latent Viral infections

• All of these viruses are in the Herpesviridae family

Herpesviridae Family

• Double stranded DNA (dsDNA), enveloped viruses

-herpes simplex virus type 1(cold sores)

-herpes simplex virus type 2 (genital herpes)

-Varicella-zoster virus (chicken pox, shingles)

-Epstein-Barr (infectious mono and Burkitt’s lymphoma)

Herpes Simplex virus-1

HSV-1 reactivation

Herpes simplex-1

• HSV-1 causes fever blisters, HSV-2 genital herpes

• Symptoms: fluid filled skin lesions

• Treatment: Acyclovir

Varicella (chickenpox) and Herpes Zoster (Shingles)

• HSV-3 causes chicken pox and latent activation known as shingles

• Acquired by respiratory route, 2 weeks later see vesicles on skin

• Vaccine established in 1995 for chickenpox

Epstein Barr

• Causes infectious mononucleosis

• Acquire by saliva, incubation period is 4-7 weeks

• Identify by

-lobed lymphocytes

-heterophile antibodies

-fluorescent antibody tests

Chronic infections

• Infectious virus present at all times

• Disease may be present or absent

• Examples are Hepatitis Type B and Type C viruses

Type Hepadnaviridae family: Hepatitis B• dsDNA virus, enveloped• Hepatitis B

-passes through intermediate stage (RNA) for replication-three particles found in blood sample1. Dane2. filamentous3. sphericle-exposure through blood/body fluids

Replication of Hepatitis B

Hepatitis Type B

• Incubation period is ~12 weeks

• 10% of cases become chronic, mortality rate is less than 1%

• About 40% of the chronic cases die of liver cirrhosis

Flaviviridae Family: Hepatitis Type C

• Hepatitis C virus– (+) ssRNA virus, enveloped– Obtain from blood/body fluids– Incubation period averages 6 weeks– Hard to screen blood for the virus– 85% of all cases become chronic

What other types of Hepatitis viruses are known to infect humans?

• Hepatitis Type A– Found in the Picornaviridae family (+) ssRNA

-obtain through fecal-oral route, enters GI tract and multiplies

-incubation period is ~4 weeks

-symptoms include: anorexia, malaise, nausea, diarrhea, abdominal discomfort, fever, and chills lasting 2-21 days

Slow Infections

• Infectious agent increases in amount over a long time during which there are no symptoms

• Examples are HIV found in the Retroviridae family

• Retroviruses use reverse transcriptase to replicate ssRNA

Retroviridae-multiple strands of (-)RNA

• HIV

-infects Helper T cells

-requires the enzyme reverse transcriptase

-integrates as a provirus

-is released by budding, or lyses the cell

HIV replication

Viruses associated with cancers

Viruses and tumors

• dsDNA viruses are most common to cause viral-induced tumors

• Cancer is result of integration of viral genes into the host chromosome

• Transforming genes are called oncogenes

• Examples: papillomavirus, herpesvirus

Orthomyxoviridae-multiple strands of (-)RNA

• Influenza virus– Consists of 8 segments of RNA– Envelope has H spikes (hemagglutinin) and N

spikes (neuraminidase)– Incubation is 1-3 days– Symptoms include: chills, fever, headache,

muscle aches, may lead to cold-like symptoms

Influenza virus

If multiple forms infect one cell…reassortment can

occur

Antigenic shift vs antigenic drift

Ways to study viruses

• Since viruses grow in living cells….need a live cell to culture them– Cell culture/tissue culture– Embryonated chicken eggs

Cell Culture

Proteinaceous infectious particles: PRIONS

• 1982 Stanley Prusiner proposed that there were infectious proteins

• Caused the disease “scrapie” in sheep

• Caused the “mad-cow”disease in 1987

• Human forms suggest a genetic component

Prions

• Contain no nucleic acid

• Abnormal protein promotes conformational change to normal protein

• Results in damage to neurons…transmissible spongiform encephalopahthies

Brain with spongiform encephalopathy

Infections caused by prions

Mechanism of prion

replication

Rhabdoviridae (-)ssRNA, enveloped

• Rabies virus

-enters the skin and multiplies in skeletal muscle and connective tissue

-virus travels along nerves to the CNS causing encephalitis

Pathology of rabies