Flashcards in Major DNA viruses Deck (103):
only human parvovirus
ss, linear DNA, naked icosahedral
causes Fifth's disease - slapped cheek rash
Trans: respiratory and oral secretion
What sort of cells does B19 preferentially infect?
mitotically active erythroid precursor cells in the bone marrow
Describe the lytic phase of B19
viremia is established
viral shedding, moves out of bone marrow
flu like symptoms
Describe the non infections immune response of B19
circulating immune complexes that cannot fix complement results in erythematous, maculopapular rash, arthralgia, arthritis (last two rare)
What is important for clearing B19?
what causes common rash illness in school aged children?
lacy reticular maculopapular rash on trunk and extremities
Rash appears with IgM
what is the concern with a B19 infection in a sickle cell patient?
Aplastic crisis - drop in RBCs
concerns with Intrauterine infection of B19
hydrops fetalis or fetal death
Rash appears with IgM
How would you treat acute vs. chronic B19?
since mild - acute treat with supportive care, ibuprofen for fever and topical anesthetic or antihistamine
For chronic which can be seen in IC pts - IV immunoglobins
DsDNA - linear
respiratory trans. via inhalation of droplets or eye contact
GI trans. - fecal-oral route
Pathogenesis of Adenovirus
typically infects where comes in contact with mucoepithelium
commonly infects local lymphoid tissue - conjunctiva, adenoids, tonsils, respiratory, peyer's patches
*typically not pathogenic
Where can Adenovirus persist?
in tonsils and adenoids in childern
in intestines in adults
How does Adenovirus interfere with host defenses?
interferes by blocking IFN and T cells
Viral oncogenes of Adenovirus
lytic in nature so tumorgenesis is not concern
late proteins E1A and E1B leads to cell growth
E1A inactivates pRB (retinoblasts)
E1B inactivates p53 (mediates cell apoptosis)
What are some clinical manifestations of Adenovirus
Acute febrile pharyngitis
Acute respiratory disease
cold, laryngitis, croup, bronchiolitis, viral pneumonia
"shipyard eye" -epidemic keratoconjunctivitis
cervicitis and urethritis - rare in women
acute gastroenteritis in infants
With Adenovirus infections in childern, what symptoms would you see in infants and young children versus older children?
infants and young - acute febrile - stuffy nose, fever, sore throat
Older children - Pharyngoconjunctival fever - tends to occur in outbreaks. associated with underchlorinated pools
Notice lots of military recruits have Acute respiratory disease. Symptoms include fever, runny nose, cough and pharyngitis. A couple of infected recruits also present with conjunctivitis. What could it be?
small, circular (so has own polymerase to make DNA but use host polymerase for RNA), in nucleus, ds, non enveloped
squamous epithelial growth
HPV encodes proteins that promote
lytic infections in permissive cells
transforming, oncogenic infection in non permissive cells
What does HPV cause?
warts, condylomas, papillomas and cervical carcinomas
How long could HPV incubate?
2 weeks to 1 year
what strains of HPV could cause Anogenital warts?
6 and 11
what strains of HPV could cause Cervical carcinomaL?
16 and 18
HPV protein E1
binds DNA at ori and promotes viral DNA replication and has helicase activity
HPV protein E2
and activates viral mRNA synthesis
HPV protein E5
oncoprotein that activates the EGF receptor to promote growth
HPV protein E4
disrupts cytokeratins to promote release
E6 and E7 of HPV 16 or 18
become immortilizing genes
E6 binds to p53, activates telomerase and suppresses apoptosis
E7 binds p105RB
L1 and L2 of HPV
late structural (capsid) proteins
describe the development of papilloma
infects basal cells of dermal layer via L1 VAP/ integrins
replicates in squamous epithelium of skin(warts) or mucus membranes (genital, oral or conjunctival) -> epithelial proliferation
what is a wart ?
virus stimulation of cell growth leads to thickening of basal and prickle layers
epithelial spikes form - papillomatosis
enlarged keratinocytes with haloes around shrunken nuclei develop
Where is the HPV produced in skin layers?
in granular cells near the final keratin layer
not a lytic infection
shed from surface of epithelium
Common warts - HPV
benign self limited proliferative lesions
Benign head and neck tumors - HPV
usually solitary and rarely reoccur after excision
laryngeal papilloma most common type
causes most common tumor of the oral cavity
Anogenital Warts - HPV
condylomata acuminata occur mostly on squamous epithelium of external genitalia/perineum
Cervical dysplasia and Neoplasia - HPV
asymptomatic, may cause slight itching
appear as soft, flesh colored wart that are flat, raised or cauliflower shaped
Describe the progression of HPV medicated cervical carcinoma
infects and replicates in the epithelial cells
matures and is released as cells progress through terminal differentiation
in some cells, circular genome integrates into host chromosomes inactivating the E2 gene
expression of other genes stimulates the growth of the cell and possible progression to neoplasia
What laboratory tests can test for Cervical dysplasia caused by HPV?
cytology: koilocytotic cells (vacoulated cytoplasm)
Wart: microscopically view hyperplasia
Papanicolaou stain of exfoliated cervicovaginal squamous epithelial cells
DNA probe anaylsis or PCR (best method)
How do you treat HPV?
inteferon, imiquimod or stripping with duct tape to stimulate immune response
What sort of vaccinations are available for HPV?
Gardasil - Tetravalent (HPV-6, 11, 16, 18)
Cervarix - divalent (HPV 16 and 18)
For girls, boys and women 9-26 years
three doses: initial, 2 month booster, 6 month booster
"Herpes is forever!"
Large, ds, enveloped linear
What is characteristic of a Herpes infection?
lytic, persistent, latent and immortalizing
Describe the alpha-herpesvirinae (HSV group)
rapid cytolytic growth cycle
commonly destroy the host cell
latent in neuronal ganglia
HSV1 HSV2 VZV
Beta-herpesvirinae (CMV group)
latency non neuronal 1* lymphoreticular cells
CMV HHV6 HHV7
transmitted through saliva
Roseola rash seen on neck, trunk and thighs
Gamma-herpesvirinae (lymphoproliferative group)
replicate in mucosal epithelia
immortalized in host lymphoid cells
latency established in mucosal epithelia
transmitted through saliva and semen
in IC pts, can become opportunistic and cause cancer
What is the clinical presentation of HSV1
lesion on the oropharynx, cold sores, fever blisters
aquired in early childhood
What is the clinical presentation of HSV2
lesions on genitalia
2/3 spread from asymptomatic partners
Clinical presentation of HSV 1 and 2
vesicular lesions and shallow ulcers accompanied by fever, myalgia and malaise
What is occuring in the initial stage of HSV infections ?
virus replicates at high rates
infection resolves - within two weeks
virus travels axonally to sensory nerve ganglion and produces acute infection at ganglion
leaves episomal (circular) DNA
what occurs during HSV reactivation ?
stimuli causes the viral episomal DNA to produce LAT which causes the viral DNA to linearize again and to begin producing virus
What is the primary manifestion of HSV-1 in children?
primary infx of upper body
fever, malaise, lesions last 3 weeks
What is the primary manifestion of HSV-1 in adults?
Pharyngitis or tonsillitis
1 week duration
What can trigger reactivation of HSV?
stress, UV light, infection, menstruation, decreased immunity
What can suppress reactivation of HSV?
strong cellular immune response
high antibody titer doesnt prevent
What are the secondary/recurrent manifestations of HSV?
keratoconjunctivitis (HSV 1 of the eye) - 2nd MCC of corneal blindness, corneal scarring
Herpetic gladiatorium - wrestlers and burn victims
Herpetic Whitlow - fingers and hands - chiropractors
What are the differences in clinical manifestations between HSV 1 and 2?
HSV 1 - Keratoconjunctivitis, Gingivostomatitis, tonsilitis, labialis, esophagitis, tracheobronchitis, gladiatorum
HSV 2 - meningitis, perianal, neonatal HSV
both - encephalitis, oral, genital, whitlow
Complication of HSV1
What is a manifestation of Congenital/perinatal transmission of HSV?
CNS (49%), skin, eyes and oral cavity (50%)
Complication of HSV2
mostly benign and self limiting with no neurologic
Complication of HSV in Immune suppressed pts
severe mucocutaneous lesions
How would diagnosis of HSV 1/2 be done?
virus isolation from lesions
PCR of CSF for HSV encephalitis
Valacyclovir, acyclovir, famciclovir
How is Varicella Zoster virus transmitted?
acquired by respiratory droplet inhalation of close contact
What are some characteristics of the VZV infections in children and adults?
highly contagious, 90% of cases less than 9 years old
97% of adults are seropositive
more severe if primary infection occurs in adults
Reactivation of VZV results in ?
triggered by increased age and/or decreased immunity
What are complications of VZV?
superimposed bacterial infections
what is the clinical presentation of the primary infection of VZV?
fever, irritability and lymphadenopathy
What is the clincal presentation of a reactivation of VZV?
early symptoms: acute pain and redness of dermatome followed by rash
Post herpetic neuralgia
4 envelope glycoproteins containing mannose 6 phosphate (Man 6-P) bind Heparan sulphate
How is a VZV infection diagnosed?
3 types of lesions simultaneously seen:
1. Maculopapular -
Macule: flat discolored area of skin
Papule: small raised bump
Maculopapular: area that is usually red, and has small confluent bumps
2. Vesicular - bump containing clear fluid and when filled with pus = pustule
What are congenital and neonatal complications of VZV?
can cross the placenta
ranges from mild to fatal
primary infection during pregnancy leads to pneumonia
If infection of VZV during 1st 20 weeks of pregnancy, then ..
3% chance of transmission to fetus = Congenital varicella syndrome
scarring of skin
hypoplasia of limbs
CNS and ocular defects
Death in infancy is normal
If mother is infected with VZV one week before delivery then
sufficient immunity transferred to fetus
What is treatment for chickenpox?
Symptomatic, self limiting
acyclovir may help shorten duration
exclude kids from school until sixth day of rash
how is a zoster rash treated?
How is Zoster post herpatic neuralgia treated?
low dose tricyclic antidepressants
Who is the VZV vaccine recommended for?
for children 12 months of age and seronegative adults
Elderly to prevent zoster (>60 years old)
When is VZIG administered?
post exposure prophylaxis in individuals at high risk
mother with varicella 5 days before to 2 days after delivery
IC individuals with no reliable history
offers 3 weeks of protection
oral HPV vs. oral HSV?
Herpes - reddened, vesicular lesions - fluid filled
HPV - flesh colored, papular - skin growing out, skin warping, no fluid
linear, dsDNA, complex symmetry
Transmission of Pox viruses?
respiratory droplets or fomites
Molluscum Contagiosum infection
discrete pustules - smooth dome shaped papules
basophilic inclusion bodies
commonly an STD
primarily seen in children
IC/AIDs pt suffer atypical form and forms tumor like growth
Hepatits B virus
enters bloodstream and travels to liver to infect hepatocytes
Describe the replication of Hep B
includes RNA intermediate that serves as template for progeny DNA strands
so encodes reverse transcriptase (RNAd-DNA pol)
What liver pathology can results from a Hepatitis infection?
What is the structure of Hep B?
Partially dsDNA with DNA poly at the core
isohedral in shape
surrounded by core antigen which is then surrounded by surface antigen
what are the methods of transmission of Hep B?
Sexual, parental and perinatal through milk
replication of Hep B in the liver leads to ..
chronic inflammatory repsonse
CD8 cells kill viral infected cells
Clinical manifestations of HBV
multiplies exclusively in liver so continuously seeds blood
what is the Hep B incubation period?
What is characteristic of an acute HBV infection?
start with fever, rash, arthritis
Jaundice, dark urine, malaise nausea, RUQ pain
the continuous liver inflammation leads to fibrosis of the liver
what is characteristic of a chronic HBV infection?
pt did not make surface antibody
so there is constant production of virus
Immune tolerant phase of a chronic HBV infection
very high HBV DNA
ALT is normal
Immune active phase of a chronic HBV infection
HBeAg positive or negative
ALT is elevated
liver histology shows inflammation and fibrosis
What does the active HBV vaccine consist of?
HBsAg administered at 0, 1, or 6 months
Post exposure of HBV vaccine
HBIG - serum from person with high titers of antibody of HBsAg
used to prevent exposure in
infants born to infected mothers, spouses of infected patients and HCW following needle stick injury
Diagnosis of HBV
liver function test
-> aspartate, aminotransferase, alanine aminotransferase