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Flashcards in DNA Viruses II Deck (30)

Herpesviridae- more than a STD

-Herpes is a deal killer
-Herpesviruses cause a variety of human infections- chicken pox, mononucleus, birth defects, cancer


Human Herpesviruses

-8 different species
-most people are infected with >3
-infection is life-long

HSV-1 herpes simplex type 1-cold sores
HSV-2 herpes simplex type 2- genital sores
VZV- Varicella-zoster- chicken pox, shingles
EBV- Epstein Barr Virus- Mono, lymphoma
CMV- cytomegalovirs- mono, systemic disease
HHV6,7 human herpesvirus 6 and 7, roseola


Herpesvirus Life Cycle

-HVs are highly restricted to humans (not HSV)
-each HV prefers different cell types
-DNA genome enters nucleus for mRNA transcription
-viral gene expression occurs in immediate early, early, and late phases
-genome replication is by viral polymerase and accessory factors
-egress is by exocytosis


Herpesvirus Latency

-definition of HV latency: the genome is present in a cell but infectious virions are absent
-HVs establish latency in a variety of cell types before symptoms or virus replication are apparent
-the genomes are maintained for the life of the infected person
-major barrier to vaccines
HSV-1 (neuron)
EBV- B cell


Herpesvirus infections: Primary and Recurrent

-exposure and transmission to
-primary infection: children: severe to mild
-latency in neurons and lymphocytes- asymptomatic shedding
-recurrent disease (symptomatic)
-can infect people during primary infection, asymptomatic shedding, and recurrent infections


HSV-1 Disease: Primary

-spread by close contact with active lesions or asymptomatic shedding
-gingivostomatitis usually occurs in childhood
-lesions on mouth face, nose, eyes- usually above the waist, can be genital
-latency established in neurons


HSV-1 Disease: Recurrent

-tingling and itching (prodrome) may precede outbreak
-lesions on lips or inside mouth
-other sites: eyes, genitals, fingers
-triggers are fever, sunlight, hormones, stress, physical trauma
-lesions are contagious


HSV in the Brain

-HSV-1 and (HSV-2) primary infections often cause meningitis- stiff neck, headache
-recurrent HSV infections occasionally cause encephalitis- fever, neurologic symptoms
-HSV targets the temporal lobe


HSV-2 Disease: Primary

-Spread by close contact between mucous membranes (genital and/or oral)
-acquired in adulthood
-symptoms: many lesions, pain, itching, fever, malaise, headache- usually but not always below the waist
-latency established in neurons
-Double infections with HSV-1 and HSV-2 are common


HSV-2 Disease Recurrent

-prodrome: itching, tingling at lesion site a day before outbreak
-vesicular lesions appear on labia, penis, anus, mouth, eyes, etc
-lesions are contagious, but shedding and transmission can occur without symptoms
-frequency of recurrences is highly individual; ranges from never to monthly


HSV Diagnosis and Treatment

-serology or PCR can distinguish between HSV-1 and -2
-antiviral therapy can shorten infections and reduce transmission
-antiviral prophylaxis is advised for people with frequent outbreaks
-acyclovir is the parent drug, also valaciclovir (valtrex), penciclovir (famvir)


HSV Prevention

-safe sex
-avoid contact with cold sores
-chemoprophylaxis (valtrex and famvir)
-vaccines- none approved, trials of subunit vaccine failed


Primary VZV: Varicella (Chicken Pox)

-aerosol transmission- highly contagious
-latency in dorsal root ganglia neurons- latency established before rash appears
-distinctive rash- dew drops on rose petals, few to hundreds on face and trunk
-complications: Hepatitis, Encephalitis, Pneumonitis, Bacterial infection of lesions (MRSA, strep)


VZV Recurrence: Herpes Zoster (Shingles)

-more common in the elderly and immunocompromised
-prodrome: burning, itching, tingling
-outbreak occurs along a single dermatome
-lesions are extremely painful and itchy
-lesions are contagious and spread varicella to children
-complications: Bell's palsy, Posttherpetic neuralgia, retinitis


HZO: Herpes Zoster Ophthalmicus

-approximately 30% of zoster outbreaks affect the face
-all tissues of the eye can be infected and damaged during HZO
-zoster in the eye can destroy the retina, rapidly leading to blindness
-long-lasting pain is common


VZV Diagnosis and Treatment

-Diagnosis- clinical signs are distinctive, PCR, antigen, serology kits
-Treatment- not required for uncomplicated VZV, Zoster treatment only effective during first 3 days of outbreak
-Antiviral drugs- acyclovir and its derivatives are marginally effective, foscarnet is second-line therapy


VZV Prevention: Vaccines

-live, attenuated virus (Oka/Merck strain)
-varivax to prevent varicella, ages 1-50, 80-90% effective after 2 doses
-zostavax to prevent zoster, ages 50+- ~50% effective for zoster, ~90% effective for post herpetic neuralgia


Epstein Barr Virus Disease

-transmission by saliva
-EBV infects oral epithelial cells and B cells in tonsils- Latency in B cells
-EBV infects >90% of people by adulthood
-childhood infections are often asymptomatic
-older teens often have mono
-170,000 cases of infectious mononucleosis (IM) per year, 15% hospitalized


EBV Recurrences

-EBV is latent in a small fraction of B cells- immune surveillance suppresses EBV in healthy people, recurrences are linked to immunosupression
-Malignancies- Hodgkin lymphoma, AIDS-associated non- Hodgkin lymphoma, post-transplant lymphoproliferative disease, Burkitt lymphoma, Nasopharyngeal carcinoma
-oral hairy leukoplakia


EBV Diagnosis and Treatment

-infectious mononucleosis- clinical signs, serology for heterophile antibodies, blood smear for elevated WBCs and atypical lymphocytosis
-malignancies- treat symptoms (supportive care), alleviate immunosuppression, oncotherapy
-Antivirals- none
-Prevention- none


Primary Cytomegalovirus

-the spectrum of illness from CMV is diverse and mostly dependent on the host
-primary CMV infections are usually symptomatic- 50-95% people are infected by adulthood
-syndrome like infectious mononucleosis may occur- fever, lassitude, diffuse lymphadenopathy, absence of sore throat and rash from EBV IM


Congenital CMV Disease

-risk is highest when a pregnant woman has a primary infection
-~2% of pregnant women seroconvert to CMV+
-can lead to hearing loss, seizures, visions loss, microcephaly
-~10,000 cases of symptomatic congenital CMV disease each year


CMV and Immunosuppression

-AIDS patients prior to anti-retroviral therapy- CMV retinitis, gastroenteritis, pneuomonitis, encephalitis
-caused tremendous morbidity and mortality
-transplant recipients:
-recipient and donor are routinely tested for CMV
-CMV disease is frequent cause of transplant failure and patient mortality
-pre-emptive screening and prophylactic antiviral therapy are standard of care


CMV Diagnosis and Treatment

-serology, culture, PCR- some pregnant women are screened, not routine
-antiviral drugs- Ganciclovir, Foscarnet, Cidofovir
-prevention: none, live attenuated vaccine was ineffective, vaccine is highest priority in Institute of Medicine


Roseola infantum= Exanthem subitum

-HHV6b and HHV7 infect CD4+ T cells, site of latency
-transmitted in saliva
-3 day illness of high fever, followed by a faint rash on the trunk
-peak incidence at age 7-13 months
-occurs throughout the year


Roseola Diagnosis and Treatment

-diagnosis based on clinical manifestations-rule out drug allergy
-treatment: none- supportive care for fever, avoid giving antibiotics
-prevention: none, normal hygiene, day care allowed (not contagious rash)


Kaposi Sarcoma Herpes Virus

-higher prevalence in Africa and Mediterranean
-primary infectious is inapparent, may cause a rash in children


KSHV Diseases

-KSHV infects B cells and endothelial cells
-malignances associated with age and/or immunosuppression
-Kaposi sarcoma: endothelial cell proliferation
-Primary effusion lymphoma
-Multicentric Castleman's disease: lymphoproliferative disorder
-Inflammatory cytokine syndrome


KSHV Diagnosis and Treatment

-KS diagnosis by lesion appearance- rule out bacillary agiomatosis
-lymphoma diagnosis by pathology-sample blood and effusions
-treatment- no antivrial drugs, alleviate immunosuppression, supportive care and oncotherapy


Herpesviruses Overview

-infections are nearly universal, inevitable and last a lifetime
-most people live happily with their viruses
-asymptomatic shedding is the norm, not the exception
-antiviral therapy is helpful but not a cure-all
-immunosuppression is a risk for all HVs to reactivate or cause malignancy
-all fields of medicine encounter herpesviruses- pediatrics, OB/GYN, oncology, internal medicine, dermatology