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Transcript
DNA VIRUSES:
ORGANISM
Parvovirus (B19 virus)
naked icosahedral
ss linear DNA
Papovavirus
naked icosahedral
ds circular, supercoiled
DNA
Adenovirus
naked icosahedral
ds linear DNA
Poxvirus
BIG complex envelope
ds linear DNA
Herpesvirus
enveloped icosahedral
ds linear DNA
binds FGF receptor
cell-mediated immune
response multinucleated giant cells w/
intranuclear inclusion
bodies
alpha subgroup:
HSV-1, HSV-2, VZV
PATHOGENESIS / CLINICAL FEATURES
erythema infectiousum (Fifth disease): affects children between 4-12 fever,
“slapped face” rash
transient aplastic anemia: virus stops production of RBC
Human papilloma virus penetrates basal epithelial cells
1) common warts (1, 2, 4): most resolve in 1-2 years
2) genital warts (6,11): condylomata acuminata
3) cervical carcinoma (16, 18, 31, 33): intraepithelial neoplasia
E6: p53 E7: Rb  uncontrolled DNA synthesis
BK Polyomavirus: mild infection in children
JC Polyomavirus: progressive multifocal leukoencephalopathy (PML)
 in immunocompromised pts.: memory loss, poor speech, incoordination
upper respiratory tract infections in children (4, 7): coughing, sneezing,
rhinitis, sore throat, conjuctivitis can progress to lower respiratory tract pneumonia
epidemic keratoconjunctivitis (Pink Eye), gastroenteritis, hemorrhagic cystitis
only DNA virus to replicate in cytoplasm (own viral RNA polymerase)
molluscum contagiosum: small, 1-2mm diameter, white bumps w/ central dimple
respiratory aerosol or direct contact from skin lesions or fomites such as bedding
HSV-1: >90% of adults in 40’s exposed saliva
most are asymptomatic
gingivostomatitis: painful swollen gums, mucous membranes w/ vesicles
resolves in about 2 weeks; may have fever and other systemic symptoms
herpes labialis (cold sores): milder, recurrent form vesicles on lips or nose
keratoconjunctivitis: most common infectious cause of corneal blindness in
US (stain of eye shows dendritic branching pattern of cornea)
encephalitis: most common cause of viral encephalitis in US (temporal lobe):
sudden onset fever and focal neurologic abnormalities treatable
HSV-2: STD vesicles on vagina, cervix, vulva, penis
painful with burning and itching fever and inguinal adenopathy
neonatal herpes: transplacental transfer congenital defects/ encephalitis
DIAGNOSIS / TREATMENT
self-limited illness
IV immunoglobulin during aplastic
crisis
koilocytosis: dark-stained nuclei
surrounded by halo
light nitrogen (freeze)
surgery/ laser ablation
podophylin or alpha-interferon:
genital warts
live, nonattenuated vaccines against
some serotypes (4,7) used in military
enteric-coated: no pathogenesis
live, attenuated vaccinia vaccine
eradication in 1977: no carrier state,
easy recognition, single serotype
Tzanck smear: Giemsa stain
multinucleated giant cells Herpes
acyclovir: encephalitis and systemic
disease caused by HSV-1; also treatment
for genital herpes acts on viral
thymidine kinase, DNA polymerase
 shortens duration of lesions and
reduces extent of shedding of virus
HSV-1: latent in trigeminal ganglia
HSV-2: latent in lumbar and sacral
ganglia
Herpes Virus 6
Herpes Virus 8
Varicella-Zoster
Virus(VZV)
 infects respiratory
tract w/ 2-week
incubation viremia
Cytomegalovirus
(CMV)
saliva, blood, semen,
transplacental,peripartum
roseola: high fever, truncal rash in children
Kaposi’s sarcoma, multiple myeloma
Varicella (chickenpox): very contagious; often during winter and spring
 fever, malaise, headache w/ rash (starts on face and trunk)
 red base w/ fluid-filled vesicle (papulesvesiclespustulescrusts)
 may progress to pneumonia and encephalitis in adults (rare though)
Zoster (shingles): reactivation of latent VZV (stress or  cell-mediated immunity)
post-zoster neuralgia: burning, painful vesicles along course of sensory
nerves (unilateral dermatome distribution)
cytomegalic inclusion disease (transplacental or through mom’s milk): congenital
abnormalities (mental retardation, microcephaly, deafness, seizures, jaundice, etc..)
kidney histology w/ multinucleated cells w/ intranuclear inclusion bodies
reactivate in immunocompromised: CMV retinitis, pnemonia, hepatitis
Epstein-Barr Virus
(EBV)
 infects B cells via C3
receptor
mononucleosis: saliva (kissing) > 90% of adults have Ab (recovery in 2-3 wks)
 fever, very painful pharyngitis, lymphadenopathy, splenomegaly
 anorexia, lethargy prominent; hepatits and encephalitis in some patients
 early infection = milder disease
Burkitt’s lymphoma: transforms B cells children in Africa (large mass on face)
nasopharyngeal carcinoma (China and other parts of Asia)
oral, hairy leukoplakia (seen in AIDS patients)
Hepadnavirus (Hep B)
enveloped icosahedral
ds incomplete circular
DNA (fragments)
blood, sex, perinatally
enveloped: more prone
to environment
RNA-dependent DNA synthesis: mRNA made used as template for genome DNA
necrosis and inflammation of hepatocytes: cytotoxic Tcells
 risk of hepatocellular carcinoma
long incubation (10-12 weeks)
HBsAg: envelope protein indicating live virus and infection
anti-HBcAg: acute IgM
chronic IgG anti-HBsAg: for immunity
HBeAg: indicator of transmissibility
live, attenuated VZV vaccine
VZ immunoglobulin as prophylaxis
for immunocompromised patients
acyclovir (acting through TK)
Reye’s syndrome: encephalopathy
and liver degeneration (assoc. w/ VZV
and influenza B, esp. if with aspirin)
VZV: latent in dorsal root ganglia
ganciclovir: treat CMV retinitis and
pneumonia for AIDS patients
foscarnet: more side effects
resistant to acyclovir (no TK)
latent in WBC’s and kidney
atypical CTL’s
heterophile antibody: cross-reacts w/
and agglutinates sheep RBC’s
IgM to viral capsid antigen (VCA):
used in diagnostic test
”window period” of no HBsAg or
HBsAb; only HBcAb
active immunization: HBsAg protein
infant at birth, 2, 4, 15 months
3 shots: teens and health workers
RNA VIRUSES:
ORTHOMYXOVIRUS
Influenza virus
segmented (-) ssRNA
RNA-dependent RNA
polymerase progeny
RNA made in nucleus
enveloped helical
respiratory droplets
PARAMYXOVIRUSES:
Parainfluenza virus
HA (+) NA (+)
Respiratory Syncytial
Virus (RSV)
HA (-) NA (-)
Measles
HA (+) NA (-)
Mumps
HA (+)
NA (+)
TOGAVIRUSES:
Rubella virus
ss (+) RNA (+) HA
enveloped icosahedral
RHABDOVIRUSES:
hemagglutinin interacts w/ sialic acid receptors on cell endocytosis
 uncoating acidification via M2 protein
neuraminidase cleaves neuraminic acid on cell surface release of RNP
EPIDEMICS:
antigenic drift: viral replication mutations in proteins (every year)
antigenic shift: rearrangement of segments major changes (every 10 years)
24-48 hr incubation: fever, myalgias, headache, cough; vomiting, diarrhea rare
secondary bacterial pneumonia: S. aureus, S. pneumoniae
one piece of ss (-) RNA only (+) RNA have infectious geome enveloped
RNA-dependent RNA polymerase fusion protein:  multinucleated giant cells
Croup: acute laryngotracheobronchitis (larynx, trachea, bronchus) in children < 5
airway narrowing stridor (wheeze), barking cough, hoarseness
fusion protein: produces multinucleated giant cells (syncytial cells)
#1 cause of pneumonia in young children (esp. infants < 6 months of age)
outbreaks every winter in hospitals and communities
prior to rash, prodromal illness: after 2 week incubation fever, conjuctivitis
(photophobia), rhinitis, coryza, hacking cough, malaise (feeling cruddy)
Koplik’s spots: bright red lesions with blue-white centers on buccal mucosa
rash: 2 days later maculopapular (bumpy) from face down to lower limbs
complications: pneumonia, bacterial otitis media, encephalitis (subacute
sclerosing panencephalitisfatal CNS disease), myocarditis
infects upper respiratory infect disseminate to parotid glands (pain), ovaries,
testes (orchitis sterility if bilateral), pancreas, and in some cases, meninges
amantadine (inhibits uncoating):
treat/ prevent only influenza A (not B)
mainly elderly, unimmunized pts.
also, derivative: rimantadine
vaccine: killed influenza A and B
Reye’s syndrome: encephalitis and
liver disease in children w/ influenza or
chicken pox given aspirin
alpha virus: mosquito-borne fever, headache, encephalitis (EEE, WEE)
rubivirus: rubellaincubate 2-3 wks mild febrile illness with rash (3d measles)
congenital rubella syndrome: infect during 1st trimester teratogenic effects
heart (patent ductus arteriosus), eyes (cataracts), brain (deafness, retardation)
attaches to acetylcholine receptor on cell surface infects sensory neurons and
posterior auricular lymphadenopathy
adults (esp. women): polyarthritis
IgM: recent infection IgG: immunity
live, attenuated vaccine (MMR)
Negri body (eosinophilic cytoplasmic
limited (from IgA and IgG) immunity
from previous infections
ribavirin (effectiveness uncertain)
live, attenuated vaccine part of
MMR vaccine
not give before 15 months of age
since maternal Ab can neutralize virus
live, attenuated vaccine part of
MMR vaccine at 15 months of age
Rabies virus
ss (-) RNA
lipoprotein envelope
bullet-shaped capsid
infects all mammals
(raccoons, skunks, bats)
moves by axonal transport to CNS rapid progression to death over 1-2 weeks
REOVIRUSES:
Rotavirus
ds segmented RNA
naked helical capsid
PICORNAVIRUSES:
Enteroviruses:
infect enteric tract
Poliovirus
”infectious RNA”
limited to primates
fecal-oral: oropharynx
Coxsackieviruses
fecal-oral route
respiratory aerosol
both can cause aseptic
meningitis, mild paresis,
and transient paralysis
Echoviruses
fecal-oral route
Hepatitis A virus
fecal-oral route
rarely via blood
viral gastroenteritis: profound dehydration, esp. in infants
 fever, abdominal pain, vomiting, diarrhea (no blood, no pus)
 > 50% of infant diarrhea requiring hospitalization in U.S.
IV fluid replacement
ss (+) RNA
naked icosahedral nucleocapsid
3 serologic (antigenic) types (little cross rxn: need Ab against all 3 types)
infects Peyer’s patch in small intestine and motor neurons in anterior horn
1) mild febrile illness headche, nausea/vomiting, sore throat resolves in most
2) aseptic meningitis 5-10 days later (fever, stiff neck, headache)
3) paralytic poliomyelitis (flaccid asymmetric paralysis w/ painful muscle spasms)
possible respiratory paralysis in older patients death
group A: herpangina vesicular pharyngitis w/ fever, vomiting, malaise
hand-foot-and-mouth disease (fever and vesicular rash)
group B: pleurodynia (epidemic myalgia) fever, pleuritic chest pain
myocarditis/pericarditis chest pain, arrhythmias, cardiomyopathy,
and heart failure (> 50% of viral causes)
diabetes (possible role in juvenile diabetes in humans)
one of the leading causes of aseptic (viral) meningitis
enteric cytopathic human orphan
also, “cold” rashes
young children most frequently infected
common outbreaks: fecally contaminated water or food (ie. raw oyster)
nasuea/vomiting, fever, anorexia, jaundice dark urine, pale feces,  AST/ALT
most cases resolve spontaneously in 2-4 weeks w/ short incubation (3-4 wks)
> 100 serologic types
acid-labile
Naked: stronger, less vulnerable!
inactivated polio vaccine (Salk) w/
formalin-killed viruses: IV injected
live attenuated poliovirus (Sabine):
oral vaccine (preferred in US)
induces secretory IgA to protect
reversion virulence possible!!
Rhinoviruses:
prodrome: nonspecific symptoms fever, headache, sore throat, fatigue, nausea,
anorexia, painfully sensitive nerves around healed wound site
encephalitis: hyperactivity, agitation confusion, lethargy, seizures, madness
hydrophobia (painful spasm of throat muscles upon swallowing), foaming
inclusions inside infected neurons)
vaccination of dogs, cats
confine animals X 10 days signs?
kill animal Negri body in brain?
preexposure vaccine and human
rabies immunoglobulin (RIG)
no treatment or vaccine
enteroviruses are most common
cause of non-bacterial (aseptic)
meningitis in U.S.
Ig M antibody or 4X  in IgG
active immunity: inactivated HAV
passive immunity: preformed Ig
common cold: Coronaviruses,
(common cold)
best at 33 C
ARBOVIRUSES:
Togavirus
ss (+) RNA
enveloped icosahedral
Flavivirus
ss (+) RNA
enveloped icosahedral
Bunyavirus
ss (-) segmented RNA
enveloped helical
Calciviruses
ss (+) RNA
naked icosahedral
Deltavirus
Arenaviruses
ss circ. (-) RNA (2 seg)
enveloped helical
Filoviruses
ss (-) RNA filaments
highly pleomorphic
Coronavirus
ss (+) RNA
enveloped club-shaped
respiratory
fingernose/eye
incubation of 2-4 days sneezing, nasal discharge, sore throat, cough, headache
transmitted by blood-sucking arthopods fever, encephalitis
alpha virus (western/eastern equine encephalitis: WEE, EEE rural U.S.)
EEE more sever than WEE sever headche, nausea/vomiting, seziures, coma
rubivirus (rubella)
PLEASE SEE ABOVE
hepatitic C: milder form of hepatitis B
Yellow fever (Panama canal workers): hepatitis, fever, backache
Dengue fever (“breakbone fever”): muscle/joint aches, headache, hemorrhage,
thrombocytopenia, septic shock endemic in Caribbean
St. Louis encephalitis Japanese encephalitis (most common epidemic enc.)
California encephalitis
Rift Valley fever
Hanta virus (Korean hemorrhagic fever): hemorrhagic fever with renal failure
 also, hantavirus pulmonary sydrome: high fevers, myalgias, cough, nausea/vomit
Adenoviruses, Influenza C virus,
Coxsackieviruses
Hepatitis E: enterically-transmitted (fecally contaminated water); like Hep A
monsoon flooding
endemic to Asia, India, Africa, Central America
Norwalk virus: outbreaks of gastroenteritis in schools, camps, cramped quarters
Hepatitid D ss (-) RNA enveloped helical capsid co-infection w/ Hep B
lymphocytic choriomeningitis virus: aseptic meningitis
Lassa fever virus: severe, often fatal hemorrhagic fever w/ multi-organ
involvement (lungs, heart, kidneys, and brain)
Ebola and Marburg viruses: hemorrhagic fever (ie. Zaire outbreak)
 fever, headache, vomiting, diarrhea bleeding into GI intract shock and DIC
high infectious: health care workers, family members (bodily fluids)
upper respiratory tract infections common colds (20%)
 similar to Rhinovirus
Hepatitis E: no prolonged carrier state
Norwalk resolves spontaneously in
12-24 hours
fulminant hepatitis, liver cirrhosis
ribavirin to treat Lassa fever
treat w/ alpha interferon
live attenuated viral vaccine for
Yellow Fever
mosquito Aedes aegypti
ribavirin for hantavirus pulmonary
syndrome patients