Chapter 19

Viruses

Microbial Model Systems

• Are viruses living organisms?– Maybe

• The origins of molecular biology lie in early studies of viruses that infect bacteria

T4 bacteriophage attacking E. coli

• Bacteria are prokaryotes with cells much smaller and more simply organized than those of eukaryotes

• Viruses are smaller and simpler than bacteria

Virus

Bacterium

Animalcell

Animal cell nucleus0.25 µm

Viruses• Viruses were detected indirectly long before they were actually seen

• Tobacco mosaic disease stunts growth of tobacco plants and gives their leaves a mosaic coloration

• In the late 1800s, researchers hypothesized that a particle smaller than bacteria caused the disease

• In 1935, this hypothesis was confirmed by crystallizing the infectious particle, tobacco mosaic virus (TMV)

Structure of Viruses• Viruses are not cells

• Viruses are very small infectious particles consisting of nucleic acid enclosed in a protein coat and, in some cases, a membranous envelope

• Viral genomes may consist of:

1. Double- or single-stranded DNA

2. Double- or single-stranded RNA

Depending on its type of nucleic acid,a virus is called a DNA virus or an RNA virus

Capsomereof capsid

RNA CapsomereDNA

Glycoprotein Glycoproteins

Membranousenvelope RNA

CapsidHead

DNA

Tailsheath

Tailfiber

18 250 nm 80 225 nm70–90 nm (diameter) 80–200 nm (diameter)

20 nm 50 nm 50 nm 50 nm(a)Tobacco

mosaic virus(b) Adenoviruses (c) Influenza viruses (d) Bacteriophage T4

(a) Tobacco mosaic virus

20 nm

18 x 250 nm

Capsomereof capsid

RNADNA

Capsomere

Glycoprotein

70–90 nm (diameter)

50 nm

(b) Adenoviruses

capsid-

is the protein shell that encloses the viral genome; each protein subunit is a capsomere

• Some viruses have membranous envelopes that help them infect hosts

– surround the capsids of influenza viruses and many other viruses found in animals

– are derived from the host cell’s membrane, contain a combination of viral and host cell molecules

Membranousenvelope RNA

Capsid

Glycoproteins

80–200 nm (diameter)

50 nm

(c) Influenza viruses

• Bacteriophages, also called phages, are viruses that infect bacteria

• They have: – the most complex capsids

found among viruses

– an elongated capsid head that encloses their DNA

– a protein tailpiece that attaches the phage to the host and injects the phage DNA inside

HeadDNA

Tailsheath

Tailfiber

80 x 225 nm

50 nm

(d) Bacteriophage T4

DNA

VIRUS

Capsid

HOST CELL

Viral DNA

Replication

Entry into cell anduncoating of DNA

Transcription

Viral DNA

mRNA

Capsidproteins

Self-assembly ofnew virus particlesand their exit from cell

• Viruses are obligate intracellular parasites,

which means they can reproduce only within a host cell

• Each virus has a host range, a limited number of host cells that it can infect

• Once a viral genome has entered a cell, the cell begins to manufacture viral proteins

• The virus makes use of host enzymes, ribosomes, tRNAs, amino acids, ATP, and other molecules

Viral Replicative Cycle

host enzymes replicate the viral genome

Reproductive Cycles of Phages

• Phages are the best understood of all viruses

• Bacteria have defenses against phages, including restriction enzymes that recognize and cut up certain phage DNA

• Phages have two reproductive mechanisms:

1. the lytic cycle

2. the lysogenic cycle

Attachment1

Entry of phageDNA anddegradation ofhost DNA

Attachment1

2

Synthesis of viralgenomes andproteins

Entry of phageDNA anddegradation ofhost DNA

Attachment1

2

3

Phage assembly

Assembly

Synthesis of viralgenomes andproteins

Entry of phageDNA anddegradation ofhost DNA

Attachment1

2

4

Head Tail Tail fibers

3

Phage assembly

Head Tail Tail fibers

Assembly

Release

Synthesis of viralgenomes andproteins

Entry of phageDNA anddegradation ofhost DNA

Attachment1

2

4

5

3

• A phage that reproduces only by the lytic cycle is called a virulent phage

The Lytic Cycle

produces new phages

digests the host’s cell wall

culminates in the death of the host cell

The Lysogenic Cycle• The lysogenic cycle replicates the phage genome without destroying the host

• The viral DNA molecule is incorporated by genetic recombination into the host cell’s chromosome; this integrated viral DNA is known as a prophage

Phage

Phage DNA

The phage attaches to ahost cell and injects its DNA.

Phage DNAcircularizes

Bacterial chromosome

Lytic cycle

The cell lyses, releasing phages.Lytic cycleis induced

or Lysogenic cycleis entered

Certain factorsdetermine whether

Lysogenic cycle

Occasionally, a prophageexits the bacterial chromosome,initiating a lytic cycle.

The bacterium reproducesnormally, copying the prophageand transmitting it to daughter cells.

Prophage

Many cell divisionsproduce a large population of bacteria infected withthe prophage.

Daughter cellwith prophage

Phage DNA integrates into the bacterialchromosomes, becoming a prophage.

New phage DNA and proteins aresynthesized and assembled into phages. temperate

phage

PhageDNA

The phage attaches to ahost cell and injects its DNA.

Bacterialchromosome Prophage

Lytic cycle Lysogenic cycle• Temperate phage only• Virulent or temperate phage• Genome integrates into bacterial

chromosome as prophage, which(1) is replicated and passed on todaughter cells and(2) can be induced to leave the chromo-some and initiate a lytic cycle

• Lysis of host cell causes release of progeny phages

• Destruction of host DNA• Production of new phages

Two key variables in classifying viruses that infect animals:

– DNA or RNA– single-stranded (ss)

double-stranded (ds)

http://en.wikipedia.org/wiki/Baltimore_classification

DNA

RNA

HPV

Retroviruses• The broadest variety of RNA genomes is found in viruses

that infect animals

• Retroviruses-use reverse transcriptase to copy their RNA genome into DNA

• Human immunodeficiency virus (HIV) is the retrovirus that causes acquired immunodeficiency syndrome (AIDS)

Class VI. ssRNA; template for DNA synthesis

HOST CELL

reverse transcriptase- catalyzes the synthesisof a DNA strandcomplementary to the viral RNA and a second DNA strandcomplementary to the 1st

Viral RNA

RNA-DNAhybrid

DNA

NUCLEUS

ChromosomalDNA

Provirus

RNA genomefor thenext viralgeneration

mRNA

New HIV leaving a cell

HIV entering a cell

0.25 µm

HIVMembrane ofwhite blood cell

The viral DNA that is integrated into the host genome is called a provirus

Unlike a prophage, a provirus remains a permanent resident of the host cell

The host’s RNA polymerase transcribes the proviral DNA into RNA molecules

The RNA molecules function both as mRNA for synthesis of viral proteins and as genomes for new virus particles released from the cell

Viral Disease

• Diseases caused by viral infections affect humans, agricultural crops, & livestock worldwide

• Viruses may damage or kill cells by causing the release of hydrolytic enzymes from lysosomes

• Some viruses cause infected cells to produce toxins that lead to disease symptoms

• Smaller, less complex entities called viroids and prions also cause disease in plants and animals

Vaccines

• vaccines-

are harmless derivatives of pathogenic microbes that stimulate the immune system to mount defenses against the actual pathogen

– can prevent certain viral illnesses• Hepatitis B, A

• Polio (IPV)

• Rotavirus

• MMRV- Measles, Mumps, Rubella, Varicella (chicken pox)

• HPV

Other crucial childhood vaccines that protect against bacteria: DTaP (Diptheria, Tetanus, Pertussis [whooping cough]) Hib (Haemophilus influenzae type b) Pneumococcal

HIV can be treated

with the drug AZT.

AZT has a 100- to 300-fold greater affinity for the HIV reverse transcriptase, as compared to the human DNA polymerase

http://en.wikipedia.org/wiki/Zidovudine

antiviral drugs- can help to treat, though not cure, viral infections by interfering with viral replication

Viral infections cannot be treated by antibiotics