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, X174) 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 47 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
ds DNA
mRNA transcribed directly
ss DNA
require opposite copy
+ssRNA
behaves as mRNA
+ssRNA
reverse transcribes to dsDNA mRNA transcribed
-ssRNA
mRNA made by RNA dependant polymerase
ds RNA
Example
Poxviruses
parvoviruses
poliovirus
HIV
Influenza
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
5. Late protein synthesis
Q- antiterminator
Integrase and cI repressor
5. Replication of virus genetic material with immune host
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
mutates
evolves by natural selection
dies
Not:
no metabolism outside host
no cell structure