fexezani's version from 2015-08-21 01:31

Section 1

Question Answer
herpes- family includesmany pathogens that are capable of establishing latent, persistent, and lytic infexctions and cause a variety of diseases
most humans becomeinfected with and carry one or herpesvirus during their lifetime
genome of herpes- code forvariety of proteins that alter normal immune responses
of all herpes that infect humans onlyB originates in animals (monkey)
human herpes (HH) are divided intoalpha, beta, and gamma herpes
alpha herpesHSV-1, HSV-2, VZV, herpes B (HHV 1-3)
beta herpesCMV, HH6, HH7 (HHV5-7)
gamma herpesEBV (4), and KSHV (8)

Section 2

Question Answer
herpes consist oficosahedral capsid that contains a core with genome and nucleoptroein surrounded by tegument protein and external envelope carrying viral proteins on its surface
herpes genomedsDNA that contains 2 covalently linked sections; the unique long and unique short regions as well as inverted terminal repeats
first step of replicationglycoprotein C binds receptor on cell surface and initiates fusion that involves other viral glycoproteins
fusion of cell and viral membranes leads tointernalizaiton of virionc apsid which is transported to nuclear membrane and at nuclear pores the DNA is releaded into nucleus and transcription starts
during lytic infections3 periods of transcription->IE genes transcribed and the process is stimulated by tegument proteins
IE mRNA translated intoregulatory proteins that control further transcriptional activity
after IE proteinsE genes transcribed an dtranslated resulting in enzymes including viral DNA pol and thymidne kinase in viruses that carry the gene, invovled in DNA replication
after E proteinsL genes transcribed to produce structural proteins
herpes replication follows arolling-circle mode
once all viral components are synthesizedassembly takes place in nucleus and budding occurs at nuclear membrane an new virions accumulate in ER efore release when cell lyses
vira infection does not alway result incell death / instead can have continuous production of low titers->persistent infection / also could have latency which invovles maintenance of the viral genome without repication
HSV-1 latency characterized bygeneration of untranslated mRNAs called latency-associated transcripts
EBv latency characterized byexpression of specific genes
during CMV latencyno detectable rna or protein synthesis

Section 3

Question Answer
HSV1 and HSV2 arealpha-herpes that usually cause lytic infection of fibroblasts and epithelial cells and latent infection of neurons / most adutls are infected
HSV1 usually affectsareas above waistline
HSV usually affectsareas below waistline
most infections aresymptomatic
HSV2 more likely to causeviremia and flu-like symptoms
most common expressionsoral and genital herpes but also can see herpes pharyngitis, herpetic keratoconjunctivites, herpetic whitlow (finger), herpes gladiatorum, and eczema herpeticum
fetal infection in utero is oftenfatal
blisters formed during HSV infections aredistinctive enough to make lab tests usually unnecessary but may be useful in immunodeficient patients
Tzanck smearspreparations of a scraping at base of lesion that show balooned cells and often syncytia with intranuclear inclusions (cowdry inclusion bodies)
other diagnostic methods includeelectron microscopy, IF, and PCR

Section 4

Question Answer
mechanisms involed in HSV1 and HSV2 aresimilar
initial infection involvesepithelial cells either in open areas or in mucosa
after initial infectionvirus spreads to innervating neurons and from there to ganglion
later the virusreturns to site of initial infection where it may produce vesicular lesions
disease controlled byCTLs but Ab contribute to limit spread
immune responsecontributes to pathology of HSV infection
after latency is establishedseveral stimuli may cause reactivation and result in recurrence

Section 5

Question Answer
health care workers should use latex gloves to prevent infection
condomshelp byt not always fully protective
pateints with history of HSV infections mystabstain from sexual contact while they have prodromal symptoms or lesions; the latter must be fully reepithialized
infections treated withacyclovir or one of its derivatives
acyclovir isphosphorylated by HSV encoded thymadine kinase and acts as terminator f viral DNA synthesis / some strians have beocme resistant
other drugs arevalacyclovir, penciclovir, and famciclovier
complicationsHSV2 may reuslt in meningitis / HSV1 can cause herpes encephalitis which accounts for 95% of all fatal cases sporadic encephalitus and occurs when virus spreads from trigeminal ganglion t brain through blood or by retrograde propagation along neurons (signs include massive necrosis in or oboth brain lobes

Section 6

Question Answer
VZV us an alpha-herpes and causative agent of chickenpox and shingles
VZV is similar toHSV but is smaller, replicates slower, and infects fewer cell types
chickenpox is one of the5 classic chidlhood exanthems and results from primary VZV infection
VZV infection may beasymptomatic
incubation2 weeks but variable
initial symptoms incudefever followed by maculopapular rash more severe in trunk than limbs
each lesion develops tobecome a vesicle-the hallmark of varicella- and later beomes pustular and crusts->fianlly scabbed lesions appear
infeciton of adults often results inimmune-mediated interstitial pneumonia that may be fatal
VZV reactivation and migrationt o ksinduring adulthood ruslts in shingles or zoster
distribution of vesicles inshinglesfollows characteristic band pattern frequently in thorax) / the area innervated by the infected neurons become spainful and skin breaks with vesicles similar to chickenpox (dermatoma)
zoster mostc ommon inelderly patients and other individuals with weak immunity
skin vesicles arecharacteristic enough to diagnose both chickenpox and shingles
tzanck smears showcowdry inclusions and syncytia
Ag and Ab detecitonELISA
sensitive method to diagnose VZVPCR

Section 7

Question Answer
portal of entryresp system where the virus replicaes and spreads through liver, spleen and lymphatic systems to the skin
vira transmisison is primarilycell to cell except in skin lesions
virus migrates fromepithelial cells in skin to neurons and ganglia where it becomes latent
bothcell mediated and Ab mediated immunity are important to control spread and limit disease
pathological featurs are due to great extent toimmune response and thus adult infeciton is more severe than infection of chidlren and infants
prophylaxis and treatmentvery effective live-attenuated vaccine for chickenpox and for zoster where composition is the same but dosage is different

Section 8

Question Answer
adverse vaccine effectsmost common is soreness, swelling at site, fever, mild rash / less common is seizures / rare is cerebral ataxia and penumonia
contraindicationsallergy to gelatin, neomycin, or previous dose of vaccine / pregnancy
efficiacy85-90% / remaining % have limited symptoms and compications / at least 20 years
acycloviractive against VZV but VZV is less sensitive
immunosuppresed patients may be treated withvaricella-zoster Ig prepared from sera os seropositive people / pain managed wuth analgesics or topical anesthetics
complicationsVZV can be fatal in immunocompromied people / virus capable of dissemination into multiple organs including lungs, brain, and liver / in older people postherpetic neuralgia may develop resulting in chronic pain
herpes Balpha-herpes that can be transmitted to humans / infection may be unapparent or result in vesicular lesions / transmission by bite can lead to fatal encephalomyelitis

Section 9

Question Answer
CMV is thelargest herpesvirus and belongs to beta
most adults areinfected with CMV
CMV is most common viral cause ofcongenital defects and is increasingly prevelant in immunocompromised pateints in which it establishes opportunistic infections
clinical outcome of CMV varies with age of patient and immunological status
bya dulthoodlarge fraction of population carries the virus
newborns1% infected in utero and 10% show symtpksm including small size, thrombocytopenia, microcephaly, intracerebral calcification, hepatosplenomegaly, and rash known as cytomegalic inclusion disease
perinatal infeciton usuallywithout clinical manifestations
in adults CMV is asexually transmitted disease, usualyl asymptomatic but osme patients may develop mononucleosis with symptoms similar to those of EBV infection but pharyngitis and lyphadonopathy are less severe or absent
immunocompromised patients are at high risk forpneumonia, retinits, and colitis
CMV may causerenal transplant failure
diagnosed by ELISA testing for presence of IgM for in utero or IgG
virus can be isolated fromblood, urine, saliva, and propogate din human fibroblasts
histologyvery characteristic and shows enlarged cells containing owl eye inclusions
also useful for diagnosis areIF and PCR

Section 10

Question Answer
pathogensis of CMV issimilar to that of other herpesviruses and infections are often inapparent
virus transmitted bymost bodily fluids and secretions and is capable of establishing persistent infection or latency in T cells and macrophages
spread occurs wheninfected cells travel throughout the body
infected individuals shed virus in bodily fluids intermittently for life
reactivationoften with severe consequences usually follows immunosupression
vaccineonly has efficacy in patients after renal transplant
maternal Absdo not confer protection
ganciclovirinhibits viral DNA synthesis / also can use valganciclovir, cidofovir, and foscarnet / mechanism same as ACV->activated when phosphorylated by CMV encoded kinase (not thymidine kinase so ACV has limited efficacy) and act as terminators of DNA synthesis
cidofovir is acytidine analog that does not require phosphorylation to be active
foscarnetinhibits DNA pol by mimicking the pyrophosphate in dNTPs
complicationscan udnergo reactivation form leukocytes particularily during immunosuppression

Section 11

Question Answer
herpes 6 and 7 found in80-91% of pop
hH6 has2 variants, HHV6A and HHV6B
HHV6 and HHV7 arebeta herpes that nearly universally found in human pop
HHV6 associated withone of the classic childhood exhanthems: exanthem subitum or roseola characterized by high fever an short-lived nu generalized rash in 30% of infections
HHV7 may causemononucleosis and lymphadenoathy

Section 12

Question Answer
EBV belongs togamma herpes and is transmitted by saliva
EBV typesA and B with different geographical distributions although both may be found in same patient
main characteristic of EBV isability to immortalize cells
EBV has alimited host range and tissue tropism
important EBV proteinsearly antigen (EA), viral capsid antigen (VCA), nuclear antigens (EBNA)m and glycoproteins of the membrane (MA)-> these provide the basis for diagnosis

Section 13

Question Answer
EBV infection common syndromesinfectious mononucleosis (glandular fever, kissing disease) which is milder in children / accompanied by fatigue, lymphadenopahy, splenomegaly, and exudative pharingitis / high fever is frequent and rash is possible
in people with low immunityEBV infection can be life threatening and induce several lymphoproliferative diseases inclduign african burkit lymphoma, hodgkin lympohma, and nasopharyngeal carcinoma
rare result of EBV infection ishairy oral leukoplakia which results in mouth lesions
diagnosis of infectious mononucleosis is based onsymptoms bt lab tests may include lymphocyte counts, presence of downey cells, and heterophile Ab (monospot)
heterophile Abs arenon-soecific but they recognize protiens on surface of sheep and other animals (paul-bunnel antigen) / not a good test for children
antigens useful for diagnosisEBNA, EA, MA, and VCA
also can be employed PCR

Section 14

Question Answer
EBV infectsepithelial cells but ost problems are result of infection of lymphocytes
disease is product ofan inapproprate immune response which is result of viral proteins sych as an IL-10 analogue
EBV mayactivate B cell growth and prevent apoptosis which may reuslt in lymphoma
T cella ctivationa nd proliferation leads tolymphocytosis and malaise
T cell appearanceDowney cells and become 10-80% if the total WBC count
EBV does not code forthymidine kinase so ACV is not useful
treatment and vaccinenone
complicationsrecurring replication can result in disease similar to chronic fatigue syndrome
EBV can causeneurological complciations and rupture of spleen (spleen rupture cna be avoided by instructing patient to rest)

Section 15

Question Answer
KSHV is not onlylinked to kaposi sarcoma but also with other proliferative disorders
while KS is often associated with HIV-1 infection the disease was known before the AIDS pandemic
prevalence of KS is particularly high amongelderly men of mediterranean (jewish and italian) and easten european ancestory
KSHV mainly transmitted bysexual contact but non sexual transmission is possible
most primary infections areasymptomatic and disease is result of viral reactivation
KSHV can result inlung infection
tumors originate due toimmortalization of endothelial cells at mutliple sites
diagnostics based onsymptoms, PCR, and serology