Enveloped DNA Viruses - Microbiology Block 2

Enveloped DNA Viruses  MODULE REVIEW *We won’t cover Hepadnaviruses today, during Hepatitis lecture later WHY SHOULD YOU CARE? ENVELOPED DNA VIRUSES HSV-2 estimation 2012, ASM WHY YOU SHOULD CARE CLASS OBJECTIVES  Be able to differentiate naked & enveloped DNA viruses...

Enveloped DNA Viruses  MODULE REVIEW *We won’t cover Hepadnaviruses today, during Hepatitis lecture later WHY SHOULD YOU CARE? ENVELOPED DNA VIRUSES HSV-2 estimation 2012, ASM WHY YOU SHOULD CARE CLASS OBJECTIVES  Be able to differentiate naked & enveloped DNA viruses, and how they differ from RNA viruses in terms of structure, replication, morphology, etc. (ongoing)  Be able to compare & contrast naked & enveloped DNA viruses (last class & today)  Be able to distinguish which viruses are enveloped DNA viruses and the diseases they cause  Be able to diagnose the enveloped DNA viruses based on signs, symptoms, diagnostic tests  Be able to prescribe appropriate prevention and treatments including available vaccinations & therapeutics  What is the herpesvirus not naturally found in human hosts that can cause disease?  Useful website: https://www.amboss.com/us/knowledge/General_virology ENVELOPED DNA VIRUSES Virus Family Herpesviridae Poxviridae DNA Strand dsDNA dsDNA DNA Shape Linear Linear Capsid shape icosahedral Nucleosome Important HSV1, HSV2, VZV, EBV, Smallpox, Examples CMV Vaccinia VIRAL LIFE CYCLE- ATTACHMENT & ENTRY & UNCOATING  Attach & bind to their specific receptors  Changes surface proteins to allow virus to enter  Entry  Fusion- Viral envelope fuses with the host cell membrane causing the virus to enter  (Remember- Depends on pH: neutral pH= fusion occurs at cell surface, acidic pH= fusion occurs in endosome… aka endocytosis)  Endocytosis  https://www.youtube.com/watch?v=D9OtJU3F6eQ  Uncoating/Nuclear entry  Nucleocapsid of DNA viruses is usually delivered to the nucleus where uncoating occurs  Degradation by viral or host enzymes or by simple dissociation  REPLICATION, ASSEMBLY, & RELEASE  These DNA viruses replicate in the nucleus of the host cell  Double-stranded DNA (dsDNA):  Without reverse transcriptase: viral negative DNA strand is transcribed to mRNA using host cell's RNA polymerase → viral proteins and progeny dsDNA are formed  https://www.youtube.com/watch?v=fH1zS7hlW54 More detail than what is necessary for this class  Remember lytic means burst  Latent infection most commonly occurs in nerve cells  Assembly  Progeny viral DNA, early & late proteins, & capsid  Release  Envelope tends to bud out, keeping host cell alive, or exocytosis  *HSV can perform cell lysis though* TEST YOUR KNOWLEDGE #1  What are the 5 Herpesviridae we’re going to learn today? 1. Herpes Simplex Virus 1 (HSV1) 2. Herpes Simplex Virus 2 (HSV2) 3. Epstein-Barr Virus (EBV) 4. Cytomegalovirus (CMV) 5. Varicella Zoster Virus (VZV) WARNING: THERE WILL BE SOME GRAPHIC IMAGES IN TODAY’S LECTURE *sorry Karen ONLY *8* HUMAN HERPESVIRUS *EXCEPTION: MACACINE ALPHAHERPESVIRUS-1 AKA HERPES B VIRUS **ALL HERPESVIRUSES CAN CAUSE LATENT INFECTION IN SPECIFIC TISSUE ALPHAHERPESVIRUSES HERPES SIMPLEX 1 (HSV1), HERPES SIMPLEX VIRUS II (HSV2), VARICELLA ZOSTER VIRUS (VZV)  PATHOGENESIS OF PRIMARY & RECURRENT HSV & VZV  HSV 1 & HSV 2 are closely related viruses  Can be asymptomatic  Distinguishable by PCR  HSV 1 above the waist, HSV 2 below the waist*  *Exception, we’re seeing a rise in vice versa because oral sex was believed to be “safe” Signs & Symptoms: Genital Pain or itching.You may experience pain and tenderness in your genital area until the infection clears. Small red bumps or tiny white blisters. These may appear a few days to a few weeks after infection Ulcers Scabs Orofacial Tingling and itching. Many people feel itching, burning or tingling around the lips for a day or so before a small, hard, painful spot appears and blisters erupt Blisters. Small fluid-filled blisters typically erupt along the border of your lips. Oozing and crusting  MUCOCUTANEOUS LESIONS CAUSED BY HSV A. Primary gingivostomatitis with multiple eroded lesions B. Recurrent infection with lesions on the vermilion border of the lip and beyond C. Multiple grouped erosions on an erythematous base on the penis D. Lesions on the uterine cervix. TRIGGERS  SKIN LESIONS CAUSED BY VZV  A. Chickenpox lesions on the back of a child (primary disease)  B. Zoster in a child who presented with 6 days of eye pain and a rash in the distribution of the ophthalmic branch of the trigeminal nerve  C. A linear eruption of zoster that could be mistaken for poison ivy  D. Zoster around the trunk in an immunocompromised patient  DIAGNOSIS, TREATMENT, & PREVENTION  Diagnosis  Usually PCR of skin scrapings  Prevention  Safe-sex education & condoms & dental dams with HSV1 & HSV2  *Vaccine??? TBD. See: Also a Scientist  Live, attenuated VZV vaccine prevents chickenpox in normal & some immunologically impaired children  *Considerations: immunodeficient children not candidates for vaccine, but can be given human immunoglobulin after exposure  Treatment  Acyclovir- Nucleoside analogue, Oral pill  Penciclovir- Nucleoside analogue, Topical application BETA- & GAMMAHERPESVIRUSES  CYTOMEGALOVIRUS INFECTION (ESP. CONGENITAL)  from the Greek cyto-, "cell," + megalo-, "large"  ~50-80% of adults in US have had a CMV infection by age 40  Permanent, Latent  Infects epithelial cells, monocytes/macrophages, T cells.  Can be transmitted in bodily fluids (urine, tears, saliva, blood, semen, cervical secretions, breast milk) even in patients with dormant infectious; albeit not highly contagious  Usually harmless, unless pregnant or immunocompromised A. Infant with severe congenital CMV with stigmata of disease including petechial rash, microcephaly, jaundice, and abnormal posture of the upper extremities secondary to central nervous system (CNS) damage. B.Computerized tomographic image of an infant with CNS damage secondary to congenital CMV with severe periventricular calcifications (white signal lining ventricles) and ventriculomegaly.  EPSTEIN-BARR VIRUS (EBV) AKA “KISSING DISEASE”  One of the most-common human viruses  Spread through bodily fluids  Kissing  Sharing drinks & food, cups, utensils, toothbrushes  Having contact with drooled-on toys  Can cause infectious mononucleosis (“mono”)  Usually asymptomatic in children, mild, illness in teens & adults. Mono can last several months. Watch for splenomegaly  Can affect central nervous system & cause encephalitis, meningitis, & Guillain-Barre syndrome (Rare- Autoimmune & attacks nerves)  Linked to autoimmune diseases (fibromyalgia) & cancer  Hodgkin’s Lymphoma- Usually upper body. Lymphatic system. Most treatable  Burkitt’s lymphoma (Non-Hodgkin’s)- Anywhere in body. Lymphatic system. Rare & aggressive.  PREVENTION & TREATMENT  Diagnostics  PCR  Antibody tests in EBV, but not always reliable because it might not differentiate current or past infection  Prevention*  Prophylactic antiviral therapy- before organ transplant to prevent viral reactivation due to compromised immune system  Preemptive antiviral therapy- administering antivirals after monitoring viral loads. Start to rise? Antiviral given  Treatment  CMV-  Nucleoside analogues- Inhibits viral DNA-dependent polymerase.  Phosphonoformate aka non-nucleoside inhibitor (Foscarnet)- inhibit Genome Replication. Inhibits viral DNA polymerase.  EBV-  Nucleoside analogues (acyclovir)- but less effective against post-transplant lymphoproliferative disorders seen in EBV  TEST YOUR KNOWLEDGE #2  You were so fascinated by the discussion on Tulane Primate center and all the cool research they’re doing there, that you decide to spend a summer at their summer research program (yes, it’s paid, yes this is an #ad, no I didn’t get paid for it, yes, I’m trying to distract you with unnecessary information).You’re curious about the angry monkey face and want to see it for yourself, so on your first day, you go to the cages and make faces at a female Indian Macaca mulatta. But oh no! A technician left the cage unlocked and the primate bites you!  What herpesvirus should you be tested for after the bite?  POXVIRUSES  Have nucleosome instead of capsid  Contains DNA & surrounded by its own membrane  Unlike other DNA viruses do NOT require access to the host nucleus  Replicate in cytoplasm within compartments termed “viral factories”  POXVIRUSES  Both smallpox & monkeypox spread via bodily fluids, respiratory droplets, skin-skin contact, fomites (bedding & clothing)  Smallpox (Variola Virus)  Eradicated in 1980 due to vaccines  Last natural outbreak in the US in 1949  Monkeypox  Monkeypox causes lymph nodes to swell (lymphadenopathy) while smallpox does not SMALLPOX VACCINE *It’s gross, but it’s from 1955…. Science has come a looooooooooooooooooooooooooooooooooooooooong way since then. ALSO A SCIENTIST- HSV 2 VACCINE Lesia Dropulic, MD -Staff Clinician, Laboratory of Infectious Diseases, Medical Virology Section, National Institute of Allergy & Infectious Disease  HSV529 vaccine- HSV2 vaccine candidate  https://academic.oup.com/jid/article/220/6/990/5486075  https://clinicaltrials.gov/ct2/show/NCT01915212  Phase 1: A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to determine the drug's most frequent and serious adverse events and, often, how the drug is broken down and excreted by the body. These trials usually involve a small number of participants.