Term
| Which pathogens establish Persistent or Latent infections? |
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Definition
1) Bacteria- Mycobacteria, Treponema
2) Protozoa- Plasmodium, Toxoplasma, Trypanosomes
3) Viral- EBV, HSV, CMV, VZV, HIV, HBV, HCV, HPV |
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Term
A patient presents with hemorrhagic lesions on his lips and in mouth-around the intubattion tube.
Fluid form these lesions is collected and sent for a Tzanck smear and viral culture. It comes bak with multi-nucleated giant cells.
What is this and what are the general features of its viral particle?? |
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Definition
Hemorrhagic lesions on lips/moutn with Tzanck smear + for MNGC means HSV
Humans are sole reservoir for transmission**
1) Envelope from host
2) Tegument surrounding capsid
3) Capsid (icosahedral)
4) dsDNA (linear) |
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Term
| What is the general life cycle of HSV-1? |
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Definition
Lytic
1) Attachment with heparin sulfate (HS-gB,gC) and HveA (gD) receptors
2) Entry with gD,gB and gH-dependent fusion
3) DNA replication (nuclear)
4) Assembly in inta-nuclear inclusions
5) Egression with death or lysis (except PNS neurons, where there is retrograde axonal transport to cell bodies and expression of Latency-Associated Transcript) |
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Term
| What is the relevance of Latency-Associated Transcript in HSV-1 infection? |
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Definition
1) Retrograde transport of viral particles in PNS neurons leads to persistent DNA in extrachromosomal circular episomes.
2) Within these episomes, there is no lytic expression, but there is LAT expression with no overt disease. |
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Term
| How can latent HSV-1 infections be re-activated? |
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Definition
1) Stress, UV, trauma, hormones, immune suppression causes virus to re-enter lytic cycle
2) Anterograde transport to spread from PNS to site of infection
**Asymptomatic virus shedding is VERY common |
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Term
| What virulence factors are associated with HSV? |
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Definition
1) Viral DNA synthesis (thymidilate kinase and ribonucleotide reductase)
2) Shut off host protein-syntehsis and block apoptosis (UL41 and y34.5)
3) ICP0 processing controls gene expression, toxicity and apoptosis by altering its stability in PNS neurons
4) Immune regulation- block complement, Ab and Ab recognition (gC, gE/gI and ICP47) |
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Term
| What is the basic pathogenesis of HSV infections? |
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Definition
1) Vesicular lesions with CPE and inflammation (host immune from NK cells)
2) Viral shedding with high neutralizing Ab
3) Spread to CNS is dangerous (encephalitis). |
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Term
True or False:
HSV lesions are always less severe with shorter durations in Recurrent infections. |
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Definition
False!
Usually true, but Herpetic Stromal Keratitis (HSK) (involves corneal opacity resulting from CMI response to virus-infected corneal stromal) occurs due to repeated infections. |
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Term
| How do you diagnose/treat HSV infections? |
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Definition
1) Diagnose with
- Tzanck smear for MNGC with inclusion bodies
- Direct virus isolation from tissue (slow but GOLD STANDARD)
- FISH and PCR
- Serology
2) Treat with Acyclovir or Penciclovir (topical cream) |
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Term
| What population is particular in danger of HSV-related sequele? |
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Definition
Pregnant women (5-28% shedding!)
To prevent disseminated disease in infants, you can use Cesarean delivery. |
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Term
| Which viral/bacterial pathogens are known to cause direct tumor transformation? |
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Definition
Bacteria
1) H. pylori causes Adenocarcinoma and Lymphoma
2) Bartonella quintana causes Angiomatosis
Viral
RNA) HTLV-1 (retrovirus) causes Leukemia, Sarcoma, Adult T-cell lymphoma
DNA) HBV, EBV, GPV, Pox, HHV-8 |
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Term
| What is the relationship between avian oncoretroviruses and cancer? |
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Definition
| They encode altered proto-oncogenes such as growth factors, receptors, and receptor-kinases |
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Term
| What is the relationship between HPV and cancer? |
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Definition
E6 and E7 oncogene produces inhibit tumor suppressor genes
1) E6 binds and degrades p53
2) E7 binds and sequesters Rb |
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Term
| How can Retroviruses such as LTR cause oncogenic transformation? |
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Definition
Over-expression of normal cellular proto-oncogene (c-myc) by cis-activation
Integration of promotor directly upstream of proto-oncogene |
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Term
| How does HTLV-1 cause oncogenic transformation? |
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Definition
Trans-activation of proto-oncogene (ATF/CREB)
Tax protein binds ATF/CREB sites in promotor regions. |
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Term
| How is HPV maintained/replicated in cells? |
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Definition
Papovavirus (cirular dsRNA virus) with 5-7 early genes and 2 late genes
1) Maintained in basal cells as episome (no replication/transcription)
2) Basal progress through proliferation (E gene to L-gene to virus) |
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Term
| What virulence factors are associated with HPV? |
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Definition
1) Latency in ketatinocytes
2) Transformation leading to host integration (inactivation of E1 or E2, leading to up-regulation of E6 and E7, which inhibit tumor suppressor genes). |
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Term
| What is the pathogenesis of HPV? |
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Definition
Human is reservoir
1) Integration leads to transformation resulting in hypertophy
2) Benign skin/mucosal lesions (90% from HPV6 and HPV11)
3) Metastatic disease leading to cervical carcinoma (80% HPV16 or HPV18)
- Slow-developing (70% integrated/30% episomal (E1))
- Cervical intraepithelial neoplasia..Carcinoma in Situ |
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Term
| How do you diagnose/treat HPV? |
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Definition
VACCINATE! quadrivalent Gardasil (with 6, 11, 16, 18) or bivalent Cevarix (18 and 16)
1) Biopsy for subclinical disease, PAP smear, FISH/PCR
2) For Benign skin lesions, remove if necessary for pain
For cervical cancer, use Cryotherapy (65-70%), surgery (MOST EFFECTIVE) |
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