Virus (Latin: slimy toxin, venom) Edward Jenner English, 1798

We say viruses, plural but actually should be viri

=infectious agent you could pass through a 0.2um (micrometer) filter Beijerinick 1899

I. Virus - An acellular obligate intracellular parasite with a protein capsid and a nucleic acid genome (DNA, RNA, single or double stranded)

Other acellular agents which are not viruses (see Box 14.1):

prion ,protein folded abnormally (Ex. scrapie, BSE, Creutzfeld-Jacob disease)

viroid ,smallest nucleic acid based pathogens,250bases, ssRNA circle (Ex.potato spindle tuber viroid)

Evolutionary relationships within virus families Table 14.2

Bacteriophage- virus that infects prokaryotic cells (bacteria and archaea)

Bacteriophage T4 http://www.pnas.org/content/98/20/11411/F5.large.jpg

Figure 5

An unrooted phenogram based on a 76-aa concatenated sequence from the T4-related bacteriophage major capsid proteins derived by maximum likelihood Cyanophages S-PM2 and S-PWM3 are representative of what we suggest be called the exoT-even group.

A. Size: small, from 20nm(Microviridae, fX174) to 400nm(Poxviridea, smallpox)

hard to see w/ EM(www.ncbi.nlm.nih.gov) conventional microscope (www.stanford.edu)

Genomes:5386 bases single stranded(ss) circle and 186,000 double stranded(ds) linear

Note: E.coli 4,000,000 base pairs and 3000nm long

B. Host cell specificity: most infect a single species of host cell, often relying on binding to a specific receptor: M13 phage infects E.coli F pilus and so able to infect only one subtype of E.coli , HIV attaches to CD4,CxCR4, intergrin a4b7 and CCR5 on Tcell surface proteins human only, Rabies virus attaches to nicotinic acetylcholine receptor and other conserved nerve proteins, most warm blooded animals, nerve cells

C. Life Cycle:

Virion- complete virus particle (infectious form) nucleic acid inside protein capsid

T4 Phage virion

Table 14.1 and 14.5 Types of genomes

Genome type Pathway for mRNA Example

ds DNA mRNA transcribed directly Poxviruses

ss DNA require opposite copy parvoviruses

+ssRNA behaves as mRNA poliovirus

+ssRNA reverse transcribes to dsDNA mRNA transcribed HIV

-ssRNA mRNA made by RNA dependant polymerase Influenza

ds RNA rotavirus

II. Lytic Bacteriophage Infection- leads to death of host cell, and replication of virus

Example: T4 phage, ds DNA, 170kilobase pair genome, icosahedral head, tail with tail fibers. Icosahedral (Fig 14.5) T4 mug shot Fig 14.14 Replication Cycle:

1.  attachment (adsorbsion) to LPS-core polysaccharide (wide host range: E.coli, Salmonella, Shigella, Pasturella)

2.  penetration –ATPase, expends energy

strategy to avoid restriction enzyme digestion of DNA by host: hydroxymethylcytosine-glucose to imitate methylation (restriction methylation systems are a major anti-phage defense of prokaryotes)

cut DNA at specific sequences, often palidromes

3.  early transcription 30 sec to 7 min, host polymerase and sigma 70, products: unusual T7 specific tRNA, mRNAs for proteins synthesis, DNA polymerase, RNA polymerase, ribosylation complex, sigma 70 modifying protein, T4 gp55 sigma factor, Ndd exonuclease destroys host cell DNA infection irreversibly fatal

late transcription, with Nucleic acid of T4 copied (6 min) and protein synthesis using host ribosomes (10 min) different promoters head, tails, fibers, lysozyme

4.  assembly and packaging of phage genomes as repeats, ligated (20min) maturation

5.  lysis of host cell to release virus progeny (about 200 for T4)

III. Lysogenic Bacteriophage Infection- infection does not always destroy the host cell. temperate phage is old name

Example: Lambda phage, ds DNA, 48.5 kilobase pair linear genome, icosahedral head, tail with single fiber. diagram

Fig. 14.9 Map of lambda circular due to overlapping 12 base COS sites


Fig. 14.6 Infection by a temperate phage

1.  adsorbsion – to maltose porin protein

2.  penetration

3.  a. early transcription and protein synthesis

Decision Fig. 14.9 operator right with cI. lambda repressor vs. CRO

b. delayed early (N antitermination)

4.Nucleic acid replication 4. Integration of phage genome (Prophage)

Rolling circle Integrase and cI repressor

5. Late protein synthesis 5. Replication of virus genetic material with immune host

Q- antiterminator cI repressor Prm promotor = lysogenized host

Corynebacterium diphtheria

Streptococcus pyogenes

E. coli (Shiga toxin-lamboid phage)

Clostrium botulinum

Staphylococcus aureus

6.  Assembly and packaging

7.  Lysis of host

Epilogue:SOS DNA repair system of host RecA protease accidentally cleaves cI repressor (LexA)

http://www.pris m.gatech.edu/~gh19/b1510/8lytic.jpg

IV. Animal Viruses (Table 14.3 )

Retrovirus(+ssDNA) AIDS, SIV, feline leukemia

Poxvirus(dsDNA) smallpox in humans, vaccinia, myxomavirus in rabbits

Herpesvirus(dsDNA) chickenpox, shigles, herpes cold sores, infectious mono

Orthomyxovirus(-ssRNA) influenza human, avian influenza

Rhinovirus(+ssRNA) cold

Adenovirus(dsDNA) cold, animal adenovirus tumors

Cornonavirus(+ssRNA) cold, SARS, stomach flu

V. Replication of HIV- transmission

Fig. 14.19

Identifies targets for anti-viral drugs and vaccines

  1. HIV attaches to CD4
  2. virus membrane joins cell membrane, virus uncoats
  3. reverse transciptase (in virion) makes ssDNA and
  4. viral RNA degrades
  5. dsDNA
  6. dsDNA integrates, may be maintained
  7. host RNApolymerase transcribes mRNA
  8. in cytoplasm translation of capsids, reverse transcriptase
  9. virus buds

VI. Ecological importance

Most abundant life forms in oceans (10 30 )

Approximately 15X more than bacteria and archea in oceans

Reduces by 20-40% the stock of prokaryotes each day

Kill the "winners", enhances diversity transfer genetic material, and destroy blooms

May unfortunately contribute to carbon cycling and perhaps to global warming

Philosophical Debate:

Alive: replicates Not: no metabolism outside host

mutates no cell structure

evolves by natural selection

dies