Herpesviruses Flashcards
more than an STD
- variety of human infections
- chicken pox
- mono
- birth defects
- cancer
- 8 different species
- most people infected with over 3
- infection is lifelong
Herpesvirus life cycle
- HVs are highly restricted to humans (not HSV)
- each HV prefers a different cell type
- DNA genome enters nucleus for mRNA transcription
- viral gene expression occurs in immediate early, early, and late phases
- genome replication by viral DNA pol
- egress by exocytosis-through nuclear pore and again through ER
phases of gene expression
- immediate early-proteins to help with more transcription
- early-proteins to help with replication
- late-structural proteins for virion assembly
herpesvirus latency
- definition of HV latency-the genome is present in a cell but infectious virions are absent
- 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
- HSV1 in neuron
- HCMV in HSCs
- EBV in B cell
flow chart of virus
- exposure and transmission can cause primary infection and then latency which can eventually lead to reactivation and recurrent disease
- primary infection in children and recurrence in adults can lead to primary infection of new person
- virus is shed through latency periods-can also infect a new person
HSV1 primary disease
- spread by close contact with active lesions or asymptomatic shedding
- gingivostomatitis usually occurs in childhood
- lesions on mouth, face, nose, eyes
- usually above waist, can be genital
- latency established in neurons
HSV1 recurrent disease
- tingling and itching (prodrome) may precede outbreak
- lesions on lips or inside mouth
- other sites are eyes, genitals, fingers
- triggers are fever, sunlight, hormones, stress, physical trauma, etc
- lesions are contagious
HSV in brain
- HSV1 (2) primary infections often cause meningitis
- stiff neck and headache
- recurrent HSV infections occasionally cause encephalitis by going back into brain
- fever and neuro symptoms
- HSV targets temporal lobe
HSV 2 primary disease
- 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 1 and 2 are common
HSV2 recurrent disaese
- prodrome-itching, tingling at lesion site the day before outbreak
- vesicular lesions appear on labia, penis, anus, mouth, eyes, etc
- lesions are contagious
- 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 to distinguish between 1 and 2
- antiviral therapy can shorten infections and reduce transmission
- antiviral prophylaxis is advised for people with frequent outbreaks
- acyclovir is parent drug-zovirax
- valtrex-valaciclovir
- penciclovir-famvir
HSV prevention
- safe sex
- avoid contact with cold sores-don’t kiss a baby when you have an outbreak!
- chemoprophylaxis-valtrex and famvir approved for daily use to prevent outbreaks
- no vaccines- trials failed
VZV diseases
varicella-chicken pox is primary infection
-zoster-shingles is recurrence
primary VZV-varicella
- aerosol transmission-highly contagious
- latency in dorsal root ganglia neuron
- latency established before rash appears
- distinctive rash-dew drops on rose petals
- few to hundreds on face and trunck
- complications-hepatitis, encephalitis, pneumonitis, bacterial infection of lesions (MRSA, strep)
VZV recurrence
- herpes zoster-shingles
- more common in 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-bells palsy, postherpetic neuralgia, retinitis
HZO
- herpes zoster ophthalmicus
- approx 30% of zoster outbreaks affect the face
- all tissues of the eye can be infected and damaged
- zoster in the eye can destroy the retina and rapidly lead to blindness
- long lasting pain is common
VZV diagnosis and treatment
- diagnosis-clinical signs, PCR, antigen, serology
- treatment-not required for uncomplicated VZV
- zoster treatment only effective during first 3 days of outbreak
- antiviral drugs-acyclovir and derivatives are marginally effected
- foscarnet is second line therapy
VZV vaccine
- live attenuated virus
- 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
EBV 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 per year, 15% hospitalized
EBV recurrences
- EBV is latent in a small fraction of B cells
- immune surveillance suppresses EBV in healthy people
- recurrences linked to immunosuppression
- malignancies
- hodgkin, AIDS non hodgkin, post transplant lymphoproliferative disease, burkitt, nasopharyngeal lymphoma
- oral hairy leukoplakia
EBV diagnosis and treatment
- mono-clinical signs, serology for heterophile antibodies, blood smear for elevated WBCs and atypical lymphocytes
- malignancies-treat symptoms, alleviate immunosuppression, oncotherapy
- no antivirals or prevention
cytomegalovirus
- affects everything
- primary usually asymptomatic-50-95% ppl infected by adulthood
- syndrome like mono-fever, lassitude, diffuse lymphadenopathy-no sore throat
congenital CMV
- risk high when pregnant woman has primary infections
- hearing loss
- death
- 2% of pregnant women seroconvert to CMV+
- ~10,000 cases of symptomatic congenital CMV disease each year
CMV and immunosuppresion
-AIDS patients prior to anti-retroviral therapy-CMV retinitis, gastroenteritis, pneumonitis, encephalitis, etc. caused tremendous morbidity and mortality
- transplant recipients-recipient and donor routinely tested for CMV
- CMV disease frequent cause of transplant failure and death
- pre-emptive screening and prophylactic antiviral therapy standard of care
CMV diagnosis and treatment
- serology, culture, PCR
- antiviral drugs-ganciclovir, foscarnet, cidofovir
- no prevention
- live attenuated virus was ineffective
- vaccine is highest priority in institute of medicine
Roseola infantum=exanthem subitum
- HHV6b and HHV7 infect CD4 cells, site of latency
- transmitted in saliva
- 3 day illness of high fever, followed by faint rash on the trunk
- peak incidence at 7-13 months
- occurs throughout the year
roseola diagnosis and treatment
- clinical manifestations
- rule out drug allergy
- no treatment-supportive care for fever-avoid antibiotics
- no prevention-normal hygiene
final thoughts
- 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 encounter