Lec 18 Herpesvirus Flashcards
Herpesvirus General
Family Herpesviridae
A unifying biological property of herpesviruses is their ability to persist indefinitely in their hosts by establishing latent infections that may lead to recurrent symptoms.
Latent infecitons occur after an initial infection viral DNA Is harboured in a latent state in neurons, B or T cells or other cell types.
Latently infected individuals can remain without symptoms for months or years or their entire life.
Reacttivation of latent virus can lead to recurrent disease labial or genital herpes or shingles
Herpesvirus Types
HHV-1 Herpes simplex 1 cold sores, eye and skin infections
HHV-2 Herpes simples 2 genital herpes
HHV-1 is the one you know about. HHV-2 is disgusting. HHV-3 causes chicken pocks in children. Afterwards it becomes latent and can be reactivated to cause shingles.
Shingles more common when immunocompromised (mostly older, sometimes younger)
Simian Herpes B latent in monkeys, fatal in humans! Not transmissible unless you have contact w/ monkey blood
alpha Herpes viruses functions
Variable
Latent infections come where?
alpha Herpes viruses functions
Variable host range
Short reproductive cycle: reproduce quickly
Rapid spread in culture: b/c alpha produce viruses quickly
Efficient killing of cells
Latent infections usually in nerve ganglia. No loss of nerve cells though!
Latent infecitons occur after an initial infection viral DNA Is harboured in a latent state in neurons, B or T cells or other cell types.
Latently infected individuals can remain without symptoms for months or years or their entire life.
Reactivation of latent virus can lead to recurrent disease labial or genital herpes or shingles
beta HERPES VIRUS
HIV- 5, 6, 7
beta HERPES VIRUS
HHV-5: cytomegalo, eye, brain, congenital,
HHV 6: mono-like,
HHV 7: skin rash ROSEOLA
Restricted host range
Long reproductive cycle
Slow progression in culture
Forms giant cells (CYTOMEGALIA) CELL FUSION.
Leaves viral attachment proteins on cell surface
Latent in SECRETARY GLANDS, LYMPHOCYTES
gamma HERPES VIRUS
HHV-4 Epstein-Barr: mononucleosis, cancers
HHV-8 KSAV: Kaposi’s Sarcoma occurs in HIV and
AIDS
Marek’s disease: Tumors in chickens! marek: chicken
Host range limited to NATURAL HOST
In vitro all REPLICATE in LYMPHOCYTES,
some lytic in epitheliod or fibroblast cells
Specific for B or T cells, may be latent in these
Herpesvirus infections (HSV-1)
Part 1
Acute
Primary infection at lips or eyes
Virus locally replicates at epithelium
TRIGEMINAL GANGLIA is targeted for LATENT infection, virus not detected there
Herpesvirus infections (HSV-1)
Stages of an HSV-1 infection in vivo. Humans typically acquire HSV-1 as a primary infection of the mucosa of the lips or eye.
During the initial ACUTE infection, the virus replicates locally in the mucosal epithelium and gains access to the sensory nerve termini that underlie the skin’s surface.
The virus then travels to the nerve cell bodies in the TRIGEMINAL GANGLIA where the virus will replicate in some cells and become latent in others.
Herpesvirus infections (HSV-1)
Part 2
LAT transcript still expressed
Viral Reactivation
During latent period no infectious virus is detected, and viral gene expression is suppressed, except for the LATENCY-ASSOCIATED TRANSCRIPT (LAT).
Periodically, STRESS CAUSES THE VIRUS TO REACTIVATE. During reactivation viral lytic gene transcription and DNA replication initiate in some neurons, and virions are transported back down the axons to the primary site of infection (nose or lips).
This results in infectious virus at the site of initial infection, and in some instances, clinical lesions such as cold sores will result.
HSV1 reactivation, even when multiple and recurrent, is NOT accompanied by PERMANENT SENSORY DEFICIT, suggesting that reactivation is NOT accompanied by NEURONAL CELL DESTRUCTION EITHER
Herpesvirus properties
TORIODAL (donut shaped) core in icosahedral capsid
Tegument proteins are found around icosahedral core, which play roles in reproductive cycle
Herpesvirus Properties
Large viruses range from 180 nm (HSV) to 200 nm (cytomegalovirus)
Virion composed of:
TOROIDAL (DONUT SHAPED) Core (75nm)
Icosahedral capsid (95-105nm diameter)
TEGUMENT- a granular zone of globular protein
Membrane-host lipids, viral proteins imbedded in membranes for attachment
Herpesvirus Virion structure
Tegument proteins envelop icosahedral core
Vp5 makes what?
Vp26?
Capsid
162 TUBULAR CAPSOMERES made of Vp5
Vp26 is located at the TIPS OF THE CAPSOMERS
Tegument: envelop icosahedral core
14 virus coded proteins can be involved in virus growth functions. Can also contain mRNAs
Membrane contains a LARGE ARRAY OF VIRAL GLYCOPROTEINS that act SYNERGISTICALLY to allow for ADHESION AND FUSION (penetration) of the virus and differs between members of family
Herpesvirus Virion Structure in detail
Herpes virions consist of four morphologically distinct structures, a DNA core, capsid, tegument, and envelope.
Tegument occupies the space between the nucleocapsid (capsid containing DNA core) and the envelope.
A combination of genetic, biochemical and proteomic analysis of alphaherpes virions suggest the tegument contains in the order of 20 viral proteins.
Historically the tegument has been described as amorphous but increasing evidence suggests there is an ordered addition of tegument during assembly.
Herpesvirus Genome
Large dsDNA virus, like adenovirus
Linear duplex 100 X 106 daltons
Sensitive to alkaline
The ssDNA form yields 2 loops and an internal DS segment
240 Kb codes for 84 known proteins about half are structural. Very large virus!
