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Viruses and Encephalitis

Viruses and Encephalitis. PHM142 September 24, 2019 Amy ( Yoo Im ) Choi Candice ( Zinan ) Lin Aiwen Qian. PHM142 Fall 2019 Instructor : Chesa Dojo Soeandy Coordinator: Jeffrey Henderson. What is encephalitis?. Inflammation of cranial tissue 2 major subtypes: Infection-related

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Viruses and Encephalitis

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  1. Viruses and Encephalitis PHM142 September 24, 2019 Amy (YooIm) Choi Candice (Zinan) Lin Aiwen Qian PHM142 Fall 2019 Instructor: Chesa Dojo Soeandy Coordinator: Jeffrey Henderson

  2. What is encephalitis? • Inflammation of cranial tissue • 2 major subtypes: • Infection-related • Autoimmune-mediated • Symptoms: • Ex. focal neurological deficits, seizures • Hard to identify etiological agent

  3. Viral replication DNA viruses: Herpes Simplex Virus (HSV) 1, HSV2, adenovirus RNA viruses: influenza, enterovirus, measles, rubella, mumps, rabies, arboviruses

  4. Herpes Simplex Virus (HSV) • 2 types: HSV-1 and HSV-2 • Oral vs. sexually transmitted • Route of infection: HSV-1 • Trigeminal nerve/Olfactory tract • Recurrent infection • Reactivation • Route of infection: HSV-2 • Sexually transmitted • Vertically transmitted • Latent infections in sensory neurons

  5. Herpes simplex encephalitis (HSE) • Unknown pathway to CNS target • Early diagnosis crucial • Cerebrospinal fluid PCR: • 98% sensitivity; 94% specificity • Faster vs. serologic testing • Monitoring therapy

  6. HSV Infection Intracellular Adhesion Molecule 1 (ICAM-1) Matrix Metalloproteinases (MMPs) Aquaporin 4 (AQP4) Endothelial Nitric Oxide Synthase (eNOS) Water into basal membrane Water into astrocyte Astrocyte apoptosis Cleaves tight junction proteins Nitric Oxide (NO) Brain edema Blood Brain Barrier (BBB) Disruption

  7. Treatment: Acyclovir Mechanism of Action https://www.youtube.com/watch?v=Il7WyvTlS3A

  8. Treatment: Acyclovir Mechanism of Action

  9. Summary • Encephalitis • Encephalitis = inflammation of cranial tissue • DNA or RNA viral causes • Most common viral cause of encephalitis: Herpes simplex virus • Herpes simplex virus (2 types) • HSV-1: oral-oral infection • HSV-2: sexually transmitted infection and vertical infection • Herpes simplex encephalitis • Unknown complete mechanism • CSF-PCR for diagnosis • Blood-brain barrier disruption associated with HSE • First line therapy for HSE: acyclovir (guanosine analogue)

  10. References Chaudhuri, A., & Kennedy, P. G. E. (2002). Diagnosis and treatment of viral encephalitis. Postgraduate medical journal, 78(924), 575-583. DeBiasi, R. L., & Tyler, K. L. (2004). Molecular methods for diagnosis of viral encephalitis. Clinical microbiology reviews, 17(4), 903-925.a Fodor, P. A., Levin, M. J., Weinberg, A., Sandberg, E., Sylman, J., & Tyler, K. L. (1998). Atypical herpes simplex virus encephalitis diagnosed by PCR amplification of viral DNA from CSF. Neurology, 51(2), 554-559. Liu, H.,Qiu, K., He, Q., Lei, Q., Lu, W. (2019) Mechanisms of Blood-Brain Barrier Disruption in Herpes Simplex Encephalitis. Journal of Neuroimmune Pharmacology, 14, 157-172.a Nanobot Medical Animation Studio. (2018, September 5). Acyclovir mechanism of action -3D medical animation [Video file]. Retrieved from https://www.youtube.com/watch?v=Il7WyvTlS3A Sacks S., Griffiths P., Corey L., Cohen C., Cunningham A., et. al. (2004). HSV-2 transmission. Antiviral Research, 63(1), 27-35. Silva, M. T. (2013). Viral encephalitis. Arquivos de Neuro-Psiquiatria, 71(9B), 703-709.  Stone M.J. & Hawkins C.P. (2007) A medical overview of encephalitis, Neuropsychological Rehabilitation, 17(4-5), 429-449. Tyler, K. L. (2004). Herpes simplex virus infections of the central nervous system: encephalitis and meningitis, including Mollaret's. HERPES-CAMBRIDGE-, 11, 57A-64A. Tong, S., & Revill, P. (2016). Overview of hepatitis B viral replication and genetic variability. Journal of hepatology, 64(1), S4-S16. Whitley RJ. Herpesviruses. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 68. Available from: https://www.ncbi.nlm.nih.gov/books/NBK8157/ Whitley, R. J., & Gnann, J. W. (2002). Viral encephalitis: familiar infections and emerging pathogens. The Lancet, 359(9305), 507-513.

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