Lec 9: Herpesviruses & Other dsDNA Viruses Flashcards
The herpesviruses derive their name from the Greek word_____, meaning to ____.
herpein
to creep
how many herpesviruses have been isolated from a range of hosts including mammals, birds, fish, reptiles, amphibians and molluscs?
> 100
of herpesviruses are human viruses?
8
most people in the world are
persistently infected with herpesviruses
8 Human Herpesviruses:
- ) Herpes simplex viruses 1 and (HSV-1 and HSV-2)
- ) Varicella-Zoster virus
- ) Epstein-Barr virus (EBV)
- ) Cytomegalovirus
- ) Herpesvirus 6A and 6B
- ) Herpesvirus 7
- ) Kaposi’s Sarcoma-associated Herpesvirus
Once herpesviruses have infected a host, they often remain as…
& Often…
…persistent infections for the lifetime of the host
…latent infections, which can be reactivated from time to time, especially if the host becomes immunocompromised
Both primary and reactivated herpesvirus infections can either be…
& The outcome depends on the…
…asymptomatic or can result in disease of varying severity
…interplay between the particular virus and its host, and especially on the immune status of the host.
Herpes simplex viruses 1 and 2 aka
(HSV-1 and HSV-2)
Both HSV-1 and HSV-2 infections are
lifelong
Estimated HSV-1 infection globally:
3.7 billion people under age 50
= (67%)
Estimated worldwide HSV-2 infection:
417 million people aged 15-49
= (11%)
(HSV-1 and HSV-2)
which is more prevalent?
HSV-1 (67%)
HSV-2 (11%)
…HSV-1 more prevalent
(HSV-1 and HSV-2)
initially infect…
& may enter…
…epithelial cells of the oral or genital mucosa, the skin or the cornea.
…neurons and may be transported to their nuclei, where they may establish latent infections.
2 modes of Latent infections:
- ) Virus DNA integrated into a cell chromosome. (After infection of the cell the virus genome is integrated into the genome of the host cell) (ex: retroviruses)
- ) Virus DNA present as multiple copies of circular molecules.
HSV-1 commonly infects via the…
A latent infection may be reactivated if…
Reactivation results in…
…lips or the nose between the ages of 6 and 18 months
…the host becomes stressed or immunosuppressed
…the production of virions, (which in about 20–40% of cases the virions are transported within the neuron to the initial site of infection, where they cause productive infection in epithelial cells, resulting in a cold sore)
HSV-2 usually causes…
genital herpes, which is a sexually transmitted disease.
Usually, HSV-1 infects..
& HSV-2 infects…
However, there are increasing numbers of cases where…
…face (lips),
…genitals
…HSV-1 infects the genitals and HSV-2 infects the face (backwards)
The majority of genital herpes infections (HSV-2?) produce either…
atypical or no symptoms.
Only a minority of cases are recognized
(Varicella-zoster virus) Infection usually occurs in... and causes... But, It may also spread to... and causes...
…childhood
…varicella (chickenpox).
…nerve cells, where it may establish a latent infection
…shingles
(Varicella-zoster virus) dna in host =
Extrachromosomal circular DNA
(Varicella-zoster virus)
After one got chickenpox, the virus…
Shingles occurs after…
…remains inactive (becomes dormant) in certain nerves in the body.
…the virus is re-activated in these nerves years later.
(Varicella-zoster virus) aka
“VZV”
How VZV is transmitted? (2)
- little is known, because the virus is difficult to culture in lab, and the lack of suitable animal model.
- Most likely, via skin lesions and airborne.
what detects VZV in air surrounding patients?
PCR
The reason VZV suddenly becomes active again =
Often…
= not clear
…often only one attack occurs.
(VZV)
Shingles may develop in ___ ___ ____, but you are more likely to develop the condition if: (3)
any age group
- ) age >60
- ) You had chickenpox before age 1
- ) immune system is weakened by medications/disease
Epstein-Barr virus aka
(EBV)
Epstein-Barr virus (EBV) is transmitted in
saliva
Epstein-Barr virus (EBV)
whats infected first?
then…
epithelial cells
…then infection spreads to B cells (main host cell for EBV)
main host cell type for EBV =
B cells
Usually, more than __% of people become infected with ___ during the first years of life, results in…
90%
EBV
…few or no symptoms
Epstein-Barr virus (EBV)
In developed countries some individuals…
…do not become infected until adolescence or adulthood.
Epstein-Barr virus (EBV)
Some adults develop…
infectious mononucleosis (glandular fever) aka the "kissing disease"
EBV is associated with
a number of tumors in humans
(Cytomegalovirus)
most infections show
no/mild symptoms
(Cytomegalovirus)
To a pregnant woman, the virus can infect…
the placenta and then the fetus, causing serious consequences.
(Cytomegalovirus)
In the US about __% of babies are born infected with the virus
~7% of these show evidence of…
For the other individuals, damage develops…
1%
…virus-induced damage at birth (small brain size and liver/spleen enlargement)
…at a later stage (hearing loss and mental retardation)
(Cytomegalovirus) transmission method =
sexually transmitted
Human Herpesvirus 6A/6B aka
HHV-6A
HHV-6B
Infection of a child with HHV-6B can cause
a fever and the sudden appearance of a rash.
(Human herpesvirus 7)
was first isolated from
a culture of CD4 T cells in lab
(Kaposi’s Aarcoma-associated Herpesvirus)
was discovered in ____ and is named after…
1994
…the tumor with which the virus is associated
(Herpesvirus Virion)
are relatively…
and composed of… (3)
…complex
…a large number of protein species organized into 3 distinct structures: capsid, tegument, envelope
Herpesvirus genome =
linear dsDNA
Herpesvirus capsid =
icosahedral surrounded by tegument
Herpesvirus tegument aka
Herpesvirus tegument =
“viral matrix”
= a cluster of proteins that lines the space between the envelope and nucleocapsid of all herpesviruses
Herpesvirus envelope contains
a large number of spikes
Most of viral structural proteins are commonly named
VP (virus protein)
In HSV-1 the most abundant proteins in the capsid and the tegument are
VP5 and VP16
In the herpesvirus envelope there are at least…
…12 species of glycoprotein, each of which is prefixed ‘g’
ex: gB, gC and gD
(HSV-1 genome organization)
The genome consists of…
2 unique sequences each flanked by repeat sequences
(HSV-1 replication)
Although HSV-1 infects only humans in nature, …
…a variety of animal species and cell cultures can be infected in the laboratory
(HSV-1 replication)
Entry Steps: (6)
- ) HSV-1 virion binds initially to heparan sulphate, then to main receptor
- ) virion envelope fuses with plasma membrane. (Infection may also occur by endocytosis, followed by fusion between the virion envelope and the endosome membrane)
- ) nucleocapsid and tegument proteins released into cytoplasm
- ) nucleocapsid transported to nucleus (where virus replication takes place)
- ) nucleocapsid rapidly transported along microtubules to the vicinity of a nuclear pore.
- ) virus DNA is released into nucleus (where the linear DNA molecule is converted into a covalently closed circular/complimentrary DNA molecule “cccDNA”)
(HSV-1 Tegument Proteins)
Are transported to…
Roles include…
…several sites in the cell
…a variety (down-regulation of host DNA, RNA/Protein synth)
(HSV-1 Tegument Proteins)
One tegument protein known as…
Other tegument proteins are involved in…
…virion host shutoff (vhs) protein degrades cell mRNA.
…the activation of virus genes
Herpesvirus genes are expressed in 3 phases:
immediate early (IE)
early (E)
late (L)
immediate early (IE) proteins # and role:
5 IE proteins and all are transcription factors with roles in switching on E and L genes.
early (E) proteins role:
Some of the E proteins have roles in virus DNA replication.
late (L) proteins role:
Most of the L proteins are the virus structural proteins.
Protein roles:
IE =
E =
L =
IE = transcription factors / E and L gene on switch E = virus DNA replication L = virus structure
(Herpesvirus assembly & exit) =
dsDNA is packed into procapsid in nucleus
empty shell
(Latent herpesvirus infection)
multiple genome is switched ___ during latency, but a few regions are…
off
…transcribed and a few RNAs are synthesized; some viruses also synthesize a few proteins
(Latent herpesvirus infection)
No virus proteins are required to maintain…
…latency in cells that do not divide, so none are produced in neurones latently infected with HSV-1
Virus RNAs synthesized during latency are known as
latency associated transcripts
LATs
LATs undergo…
and at least one of them plays a role in…
thereby ensuring…
…splicing
..inhibiting apoptosis
…the survival of the neuron with its latent HSV-1 infection.
increased immunocompromised =
increased likelihood of reactivation