Download Mycoviruses

Herpesviruses
100 nm
Herpesvirus structures are
unique, with tegument layer
present and genomic DNA
wrapped around core
Herpesviridae
• Large family of large, complex viruses
• Infect vertebrate hosts
• Three subfamilies:
– Alphaherpesvirinae, 2 genera
– Betaherpesvirinae, 3 genera
– Gammaherpesvirinae, 2 genera
• Very important as human pathogens
• Cause cold sores, genital herpes, chicken pox,
shingles, mononucleosis and many other diseases
• Infection is for life – herpesviruses become latent in
hosts, then reactivate
Cryo-EM shows
regular, external
structure preserved
Irregular structures often
seen in micrographs are
artifacts of distortion
from negative staining
Nucleocapsid contains
core of protein wrapped
in genomic DNA
Herpesvirus particles
• Genome: Single large segment of dsDNA, ~ 3% of
particle weight (124-235 kbp)
• Core: Nucleic acid wrapped around cylindrical
structure 25-30 nm
• Capsid: T=16 icosahedron composed of 162
capsomeres (150 hexamers and 12 pentamers),
capsid diameter 100-110
• Tegument: poorly defined material between capsid
and envelope, contains alpha trans-inducing factor (αTIP) necessary for activation of α genes and virion
host shutoff protein (VHS)
• Envelope: Derived from nuclear membrane, surrounds
tegument, has spike glycoproteins – virion diameter
120-200 nm
Major Herpesvirus structural proteins
Herpesviruses
• HHV1, Herpes simplex 1
– Cold sores, epithelial and neuronal cells
• HHV2, Herpes simplex 2
– Sexually transmitted disease (STD), also as above, teratogenic, can be
fatal in newborns
• HHV3, Varicella-zoster
– Chicken pox, shingles
• HHV4, Epstein Barr virus
– Mononucleosis, Burkitt’s lymphoma, lymphoid tissue only
• HHV5, Cytomegalovirus
– Salivary gland tropic, teratogenic, can be fatal in newborns
• HHV6, Roseolovirus
– Childhood rash, multiple sclerosis?
• HHV8
– Associated with Kaposi’s sarcoma
HSV 6,7,8 all identified
after 1990, after HIV
Biology of herpesviruses
• All specify a large array of enzymes involved in
nucleic acid metabolism
• Virus DNA synthesis and capsid assembly in
nucleus
• Production of infectious progeny is
accompanied by destruction of infected cell
• A single virus can cause several diseases
• Herpesviruses remain latent in the host for life,
and can be reactivated to cause lesions at or
near the initial infection site
HHV
genomes
Vary in size,
structure,
positions of
repeats
HHV 1 genome occurs as approximately
equal quantities of four isomers
Short and long regions of viral genome are inverted relative to
each other
Other herpesviruses may have 1, 2, or 4 isomeric DNA forms
Two models for DNA
replication of
herpesvirus; details are
still poorly understood
- DNA nicked
- DNA replication is discontinuous
- RNA primed
- by rolling circle mechanism?
Recent studies on HHV1 replication do not
support a rolling circle model, but rather a
complex set of concatameric intermediates
Human Herpesvirus 1 particles and genome
organization
Herpesvirus infection cycle
1-4.Membrane fusion, release of
tegument and VHS.
5-8. Nucleocapsids transported
on microtubules to nuclear
membrane, ejects DNA
which circularizes.
9-10. Transcription, export,
translation of immediate early
genes by cellular Pol II
11-13. Transcription, translation
of early genes; genome
replication in nucleus.
14-18. Transcription, translation
of late (structural) protein
genes; import to nucleus,
nucleocapsid assembled and
stuffed with DNA.
19-23. Nucleocapsid/tegument
buds into ER lumen; acquires
envelope, egress by fusion.
Herpesvirus packaging
• Phage-like process
• Empty particle with single
portal assembled first
• Genomic DNA stuffed through
portal
• pac1 and pac2 signals on
genomic DNA are required for
insertion of DNA through
portal and cleavage of unit
length DNA once headful is
achieved
Occurs in neurons, steps 1-7 probably like productive infection; normal viral
transcription blocked (leaky), latency-associated RNAs transcribed, spliced, 2kb
LAT in the form of lariat transported to cytoplasm, translated to LAT proteins
LAT genes are clustered;
micro RNAs regulate
LAT mRNA expression
Herpesvirus latency
Phylogenetic relationships among orthopoxviruses
Relationships among
large dsDNA viruses
Closest relatives of poxviruses are
baculoviruses, viruses the infect
insects
Closest relatives of herpesviruses
are phycodnaviruses, viruses the
infect algae