CSB351Y1 Lecture Notes - Lecture 45: Shingles, Dorsal Root Ganglion, Lymphoproliferative Disorders
26 May 2018
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Lecture 45
Summary of replication
1. Entrance through receptors, release of core virus and tegument proteins except glycoprotein and envelope left
2. Viral DNA transported into nucleus (cytoskeleton like actin help transport) and core stays outside of nucleus
3. Viral DNA circularize, temporal expression of immediate early, early genes → DNA synthesis
4. Late gene expression, producing synthesis of capsids, DNA and capsid associate and assembly in nucleus
5. Leave nucleus, collect on vesicles (some tegument proteins) and leave through golgi, cytoplasmic channels
• Model 1: Virus goes through nuclear membrane, collect pieces, golgi to exchange nuclear membranes, released
• Model 2: Virus never collects nuclear membrane but associates with golgi
• Model 3: virus goes straight through ulear pore e reall do’t ko ho irus leaes uleus ad eit
Latency of VZV
• 100nm, linear dsDNA, 125kb
• Virus enters from epithelial to nerve cells and establish latency (also found in satellite cells) – reactivated to skin
• Transmission –respiratory route (chicken pox), breathing, sneezing, virus reproduce in lungs and inter blood
- Chickenpox highly contagious but herpes zoster is less contagious (aftermath)
- 90% of people in developed countries have VZV and Zoster (shingles)is due to reactivation of VZV who had
chickenpox (individuals may not be aware of previous infection – zosters not recurrent, only 4%)
Pathology
• Varicella (chickenpox) pathology – incubate fro 2 weeks, primary infection results in viral replication in upper
respiratory and oropharynx (lesions on respiratory mucosa)
- Skin lesions occur with infection of vascular endothelial cells (rash on head, trunk, sprads to extremities)
- 100/3million deaths (Reye syndrome can occur in children who take aspirin for VZV fevers)
- Virus latent in sensory dorsal root ganglia
• Zoster (shingles) pathology – reactivation of VZV in sensory ganglia → herpes zoster (same disease)
- Inflammation and necrosis of sensory ganglia and its nerves (neural injury and cellular immune impairment)
- Skin lesions histopathologically identical to varicella (pain last weeks to several years in area of initial rash)
• Host response – varicella infections result in life-long immunity (recurrent/second episodes rare – due to
reduced humoral and cellular immunity)
• Prevention – restrict exposure, live attenuated VZV vaccine (Oka strain from guinea pig cells) but reoccurrence
could be seen, therefore, use recombinant subunit vaccine (Acyclovir, a chemotherapeutic agent)
EBV (gamma herpesvirus) – 180kb dsDNA
• Immortalizes B lymphocytes induce lymphoid malignancies in nonhuman (possible oncogenic agent in humans)
• Epstein-Barr nuclear antigen (EBNA) and latency membrane protein (LMT) are proteins expressed and required
for maintenance of latency, regulation of gene expression, control of host, etc
• Transmission – via saliva (parotides usually infected), via blood is rare, infects epithelia (primary + persistence)
- First infects pharyngeal (throat) epithelial cells) → glycoproteins on virus bind CR2 on B cells → replicated in
B cell nucleus (can be shed in saliva for 18 months, most eliminated, some virus become latent in B cells
until reactivated to be transmitted)
- B-lymphotropism due to expression of specific cell surface receptor on B cells (CD21/CR2 antigen bind EBV
and C3d of complement)
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Document Summary
Chickenpox highly contagious but herpes zoster is less contagious (aftermath) 90% of people in developed countries have vzv and zoster (shingles)is due to reactivation of vzv who had chickenpox (individuals may not be aware of previous infection zosters not recurrent, only 4%) Pathology: varicella (chickenpox) pathology incubate fro 2 weeks, primary infection results in viral replication in upper respiratory and oropharynx (lesions on respiratory mucosa) Skin lesions occur with infection of vascular endothelial cells (rash on head, trunk, sprads to extremities) 100/3million deaths (reye syndrome can occur in children who take aspirin for vzv fevers) Virus latent in sensory dorsal root ganglia: zoster (shingles) pathology reactivation of vzv in sensory ganglia herpes zoster (same disease) Inflammation and necrosis of sensory ganglia and its nerves (neural injury and cellular immune impairment) First infects pharyngeal (throat) epithelial cells) glycoproteins on virus bind cr2 on b cells replicated in.
