CSB351Y1 Lecture Notes - Lecture 44: Mononuclear Phagocyte System, Human Herpesvirus 6, Herpesviridae
26 May 2018
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Lecture 44
Herpesviridae (creep)
• Alpha – HSV-1, HSV-2 and VZV
- Short growth cycle, spread rapidly, latent in sensory neurons
• Beta – CMV, HHV-6 and HHV-7
- Long growth cycle, spread slowly, restricted host range, latent in secretory glands and lymphoreticular cells
• Gamma – EBC and HHV-8
- Growth primarily in epithelial and T/B cells, latent in lymphocytes
• Two main characteristics – 1) forms lesions 2) have latency period where viral DNA is harboured for a long time
(can be reactivated and reoccur outbreak of disease like shingles from chickenpox)
• Transmission – close personal contact, mucosal and skin surface is primary site of initial infection
- HSV1 more associated with facial lesions, HSV2 genital lesions (sexual contact)
- HSV2 transmitted mother to infant during birth via birth canal
• 150-200nm, enveloped, icosahedral particles, dsDNA linear
• Inner/outer tegument – large space between capsid and envelope, containing proteins that play role in
infection, overcoming host defence, etc (VP26, VP5 are capsid)
Temporal regulation of HSV gene expression
• HSV1 gene has at least 84 genes, certain genes expressed at different times (immediate early, early, late)
• Alpha is immediate early gene expression (promotes with identical cis-element)
- Cellular transcription factors (Oct-1, HCG-1) bind to virus (tegument-associated aTIF) to produce immediate
early transcripts (a genes)
- Viral transcription factors produced from above step and they bind to beta early genes to produce proteins
involved in viral DNA synthesis leading to HSV DNA synthesis
- Gamma late gene expression turned on to make proteins involved in virus assembly and release (from IEP)
• HSV enters cell, nucleocapsid reaches nucleus and sheds, viral DNA enters nucleus and is circularized (with
complementary regions of repeat area) by ligation or base pairing between the ends
• B genes, 3 origins of replication:
- UL9 – ori binding protein
- UL29 – ssDNA binding protein
- UL5/8/52 – helicase-primase complex
- UL30 – DNA polymerase
- UL42 – processivity factor (complex with UL30)
• HSV capsids assemble around viral scaffolding proteins in nucleus to form procapsid (help assembly)
- Autoproteolytic cleavage of scaffolding protein → mature capsid, incorporate DNA+cleavage/packaging
proteins and you have encapsidation of virus
- Full capsids associate with tegument (matrix) proteins near nuclear membrane
• Viral DNA enters nucleus of neurons, circularize and remains dormant (non-replicative)
- Transmission via skin cells (epithelial cell to ganglion of neuron)
- Latency associated transcripts (LAT) map to beta region of genome, expressed as RNAs that accumulate in
nucleus and prevent apoptosis
- Stimuli (UV, stress) induce reactivation – transported back to mucosal sites to replication and form lesions
• Latent infection → circularization of linear dsDNA, nucleosomes associate → LATs expressed from one section of
genome to maintain latency → activation induces immediate early transcripts produced → early (DNA syn) → y
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Document Summary
Herpesviridae (creep: alpha hsv-1, hsv-2 and vzv. Short growth cycle, spread rapidly, latent in sensory neurons: beta cmv, hhv-6 and hhv-7. Long growth cycle, spread slowly, restricted host range, latent in secretory glands and lymphoreticular cells: gamma ebc and hhv-8. Hsv1 more associated with facial lesions, hsv2 genital lesions (sexual contact) Hsv2 transmitted mother to infant during birth via birth canal: 150-200nm, enveloped, icosahedral particles, dsdna linear. Inner/outer tegument large space between capsid and envelope, containing proteins that play role in infection, overcoming host defence, etc (vp26, vp5 are capsid) Temporal regulation of hsv gene expression: hsv1 gene has at least 84 genes, certain genes expressed at different times (immediate early, early, late, alpha is immediate early gene expression (promotes with identical cis-element) Cellular transcription factors (oct-1, hcg-1) bind to virus (tegument-associated atif) to produce immediate early transcripts (a genes)
