Virology Lecture 07 (Part 1) PDF

Lecture 7 — Virology (Part 1) Dr. Ed El Sayed NURS 342 Objectives Virology Overview Human Papilloma Virus Herpes Viruses: Herpes Simplex Varicella Zoster Cytomegalovirus Epstein-Barr Measles General overview of viruses Obligate intracellular agents (rely on host cells for replication) Some cause no...

Lecture 7 — Virology (Part 1) Dr. Ed El Sayed NURS 342 Objectives Virology Overview Human Papilloma Virus Herpes Viruses: Herpes Simplex Varicella Zoster Cytomegalovirus Epstein-Barr Measles General overview of viruses Obligate intracellular agents (rely on host cells for replication) Some cause no clinical disease Non-living Billion of years old Loading… About 10 nonillion (10 to the 31st power) individual viruses exist on our planet Some cause acute illness Some cause chronic illness Some cause cancer - Don't require receptors specific = more ↳ need infectious compatible receptor Loading… Viral Proteins 1. Human Papilloma Virus (HPV) dsDNA virus, non-enveloped Belongs to Papillomaviridae family Sex is the primary route of transmission (most common sexually transmitted infection); skin-to-skin transmission possible (i.e. non-penetrative mucosal contact) Vertical transmission possible, but uncommon Most cases are asymptomatic and cleared spontaneously (in immunocompromised persons and HIV confection, HPV can persist) HPV is the number one cause of cervical cancer worldwide (>90% of cases) In the U.S, 13K new cases of HPV induced cervical cancer are diagnosed and 4,000 patents die of the disease every year Over 80% of the adult population will be infected with HPV during their lifetime There are over 200 genotypes of HPV HPV 6 and 11 are associated with genital warts while 16 and 18 are associated with cancer (cervical, anal, penile and oropharyngeal) The longer the duration of infection with HPV 16/18, the higher risk of cancer HIV infection increases risk of HPV associated cancer HPV is a vaccine preventable infection (1ry prevention) Screening (Pap smear/HPV DNA) is important to detect precancerous lesions (2ry prevention) There is no specific antiviral therapy (treatment for HPV associated cancer is primarily chemotherapy and surgery) HPV exclusively infects epithelial cells — gains access through microabrasions in mucosal membrane layers Infection starts in basal layer (productive entry into the cell is via endocytosis) Replication, maturation and assembly occur in apical epithelium Time between initial infection to generation of new virus is 3-4 weeks (long infectious cycle) Virulence factors include E6/E7 genes, which encode oncoprotein molecules POSTCOITAL BLEEDING IS CERVICAL CANCER UNTIL PROVEN OTHERWISE!!! Apical infections & always happen herz Loading… HPV 6/11 associated genital warts Non-cancerous * HPV 16/18 associated cancer Question The parents of a 9-year-old girl come to clinic and ask you about the HPV vaccine for their daughter. She is not sexually active. What do you recommend? A. HPV vaccine unnecessary unless she becomes sexually active B. HPV vaccine recommended now C. HPV vaccine recommended at the age of 16 regardless of sexual activity D. HPV vaccine recommended till the age of 26 2. Herpes Viruses All agents belong to the Herpesviridae family The hallmark of this family is that it establishes latency Subdivided into three main subfamilies based on where latency is established: Alpha-herpesviridae: Establishes latency in neurons — e.g. Herpes Simplex Virus 1/2, Varicella Zoster Beta-herpesviridae: Establishes latency in T-cells — e.g. Cytomegalovirus Gamma-hepresviridae: Establishes latency in B-cells — e.g. EpsteinBarr Virus A. Herpes Simplex Virus (HSV) Two types: HSV1 and HSV2 that are closely related Both viruses can infect oral and genital regions, but historically HSV1 is more common in oral lesions while HSV2 is more common in genitals Both viruses are enveloped dsDNA viruses Primary site of infection is in epithelial cells Primary infection is usually asymptomatic Recurrent infection (i.e. reactivation of virus after it established latency) is usually symptomatic Reactivation is usually triggered (i.e. a change in the immune system related in temporary loss of control of the virus — antibiotics, PMS, menopause, stress, etc…) Recurrence is usually (not necessarily always) at the site of primary infection More than 90% of adults in the US are infected with HSV1 (most infections occur in early childhood) Route of transmission of HSV1 is through direct contact with body fluids harboring the virus (mainly saliva) and indirect contact through fomites like utensils, toothbrushes Vertical transmission is mainly intrapartum (during childbirth) People with antibodies against one HSV will have a cross reaction if they get infected with the other HSV (huge similarity between HSV1 and HSV2) HSV2 primarily infects the genitals, the most common route of transmission is through sex Over 90% of infected persons do not know they are infected and transmission is mainly by undiagnosed, asymptomatic persons Symptoms of HSV1 and HSV2 include fever, cold sores, papules and infectious fluid filled vesicles that can progress to ulcers (painful) Ulcers increase the risk of human immunodeficiency virus (HIV) transmission Sores and ulcers can assume many forms Oral and perioral HSV-1 infection Genital and anorectal HSV-2 infection Herpetic whitlow HSV is not a vaccine preventable infection Treatment is focused on symptomatic relief For oral sores (HSV1), topical formulation effective, but oral therapy is better if there are severe or recurrent symptoms For genital infection (HSV2), oral formulation is necessary (topical treatment is ineffective) B. Varicella Zoster Virus (VZV) Also known as HSV3 Enveloped, dsDNA virus VZV is the only herpes virus that is transmitted via respiratory droplets Primary infection occurs in nasopharynx; virus then disseminates to other organs like spleen and liver, and latency in established in neurons Most cases of primary infection are symptomatic In majority of cases, first exposure to VZV results in chickenpox and future reactivation results in shingles (in most cases, the virus usually reactivates only once in a lifetime — in rare cases a second reactivation episode can Chickenpox — ITCHY Shingles — PAINFUL Postherpetic Neuralgia (PHN): Persistent painful symptoms after shingles rash disappears, more common in older patients and immunocompromised VZV is a vaccine preventable infection (chickenpox vaccine is given in childhood and shingles vaccine given to adults 50-years of age or older) Drugs used in the treatment of HSV and VZV inhibit viral polymerase (stops DNA synthesis) — acyclovir, valacyclovir, famciclovir In case of acyclovir resistant HSV infection, focarnet is used (nephrotoxic) C. Cytomegalovirus (CMV) Enveloped, dsDNA virus Largest virus that infects humans Also known as HSV5 The only herpes virus transmitted in utero Primary mode of infection is direct contact with bodily fluids containing the virus (breastmilk, urine, rectal and vaginal secretions, semen, blood, organ transplantation) CMV is not airborne A hallmark of infection is the histological presence of “owl eyes” — an inclusion Primary infection is usually asymptomatic in immunocompetent persons (if symptoms appear, they are usually mild, short-lived and non-specific) Latency is established in T-cells CMV is not a vaccine preventable infection Loading… CMV reactivation is a major issue in organ transplantation, which can increase risk of graft rejection In uncontrolled HIV infection, CMV retinitis is the most common end organ damage Normal fundus CMV retinitis CMV treatment: Ganciclovir/valganciclovir (DNA polymerase inhibitor) Cidofovir (DNA polymerase inhibitor) Foscarnet (for resistant CMV, nephrotoxic) Maribavir (kinase inhibitor) — for resistant CMV in renal patients, associated with dysgeusia Letermovir (terminase inhibitor) — used for prophylaxis D. Epstein-Barr Virus (EBV) Enveloped, dsDNA virus, also known as HSV4 Establishes latency in B-cells Over 90% of cases of infectious mononucleosis (aka “kissing disease”) is caused by EBV (the other 10% of cases are caused by CMV) Infection is primarily transmitted through° saliva, but other bodily fluids can transmit the virus (e.g. contact sports) O / EBV is not a vaccine preventable infection EBV infection is unique among herpes viruses because of the symptoms: lymphadenopathy, hepatomegaly, splenomegaly EBV infection in immunocompromised persons is linked to Burkitt lymphoma (primarily in outside the U.S) Vericella poster only 3. Measles ↳ resp harper. ssRNA, enveloped virus Belongs to Paramyxoviridae family Airborne and extremely infectious No specific treatment (symptomatic therapy only) Vaccine preventable infection, but… that airborne Measles rash usually starts as flat red spots that appear on the face and spread downward to the neck, trunk, arms, legs, and feet Rash inside the mouth is called Koplik spots - · 4. Respiratory Syncytial Virus (RSV) ssRNA, enveloped virus Belongs to Paramyxoviridae family Respiratory transmission via droplets (cough, sneeze) Symptoms are non-specific (body aches, fever, sore throat, runny nose, headaches, congestion) Cases increases during “RSV Season” — November thru March No specific antiviral therapy (supportive treatment) RSV vaccine for babies younger than 8-months recommended if born in “RSV Season” Recommended to vaccinate pregnant women expected to deliver during “RSV Season” — note: if mom receives the vaccine within 8-weeks of delivery, no vaccination necessary for the infant RSV vaccine for adults (60-years or older) recommended especially if there are other comorbidity (COPD, asthma, diabetes, heart disease)