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Microbiology/Immunology > DNA Viruses II > Flashcards

DNA Viruses II Flashcards

1
Q

Herpesviridae- more than a STD

A
  • Herpes is a deal killer

- Herpesviruses cause a variety of human infections- chicken pox, mononucleus, birth defects, cancer

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2
Q

Human Herpesviruses

A
  • 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

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3
Q

Herpesvirus Life Cycle

A
  • 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
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4
Q

Herpesvirus Latency

A

-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)
HCMV( CD34+ HSC)
EBV- B cell

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5
Q

Herpesvirus infections: Primary and Recurrent

A
  • 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
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6
Q

HSV-1 Disease: Primary

A
  • 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
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7
Q

HSV-1 Disease: Recurrent

A
  • 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
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8
Q

HSV in the Brain

A
  • 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
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9
Q

HSV-2 Disease: Primary

A
  • 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
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10
Q

HSV-2 Disease Recurrent

A
  • 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
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11
Q

HSV Diagnosis and Treatment

A
  • 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)
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12
Q

HSV Prevention

A
  • safe sex
  • avoid contact with cold sores
  • chemoprophylaxis (valtrex and famvir)
  • vaccines- none approved, trials of subunit vaccine failed
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13
Q

Primary VZV: Varicella (Chicken Pox)

A
  • 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)
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14
Q

VZV Recurrence: Herpes Zoster (Shingles)

A
  • 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
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15
Q

HZO: Herpes Zoster Ophthalmicus

A
  • 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
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16
Q

VZV Diagnosis and Treatment

A
  • 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
17
Q

VZV Prevention: Vaccines

A
  • 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
18
Q

Epstein Barr Virus Disease

A
  • 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
19
Q

EBV Recurrences

A
  • 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
20
Q

EBV Diagnosis and Treatment

A
  • 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
21
Q

Primary Cytomegalovirus

A
  • 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
22
Q

Congenital CMV Disease

A
  • 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
23
Q

CMV and Immunosuppression

A
  • 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
24
Q

CMV Diagnosis and Treatment

A
  • 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
25
Q

Roseola infantum= Exanthem subitum

A
  • 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
26
Q

Roseola Diagnosis and Treatment

A
  • 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)
27
Q

Kaposi Sarcoma Herpes Virus

A
  • HHV8
  • higher prevalence in Africa and Mediterranean
  • primary infectious is inapparent, may cause a rash in children
28
Q

KSHV Diseases

A
  • 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
29
Q

KSHV Diagnosis and Treatment

A
  • 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
30
Q

Herpesviruses Overview

A
  • 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

Microbiology/Immunology (46 decks)

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