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
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
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
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
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
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
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
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
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
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
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)
12
Q
HSV Prevention
A
- safe sex
- avoid contact with cold sores
- chemoprophylaxis (valtrex and famvir)
- vaccines- none approved, trials of subunit vaccine failed
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)
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
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
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
