Viruses II Flashcards
two groups of GI viruses and one e.g. for each
fecal-oral but no diarrhea (polio)
diarrhea as primary sign (restricted to gut, don’t disseminate, little cytopathology, toxin involved)
viruses that don’t cause diarrhea; characteristics
picornaviridae (enterovirus, rhinovirus)
high titers in GI trace, disseminate, asymptomatic/mild, very hardy, stable at pH 3, sensitive to Cl and formaldehyde, but HEAT-sensitive
major enterovirus syndromes
which virus causes peri/myocarditis?
mild, self-limiting illness w/rash colds aseptic meningitis pericarditis/myocarditis (COXACKIE) paralysis hepatitis
Polio
can you regain some fxn?
peak?
vaccine?
2wk incubation
causes aseptic meningitis (if 2ndary viremia high enough or persists long enough to cross BBB) or subclinical infxn
enters via Peyer’s/M cells
all enteroviruses enter this way
can regain some fxn (limb paralysis in elderly bc can’t compensate as well)
peak in late summer
yes
hepatitis A
vaccines to whom?
28 days
abd pain, fatigue, inc LFT’s, dark urine, jaundice, NV
similar sx for other hep viruses
likelihood of sx depends on age (l travelers, men sex w/men, drug users, occup risk, chronic liver disease
big syndrome assoc?
coxackie and cardiomyopathy
viruses causing diarrhea
1: rotavirus
astrovirus, norovirus (leading cause of hospitalized diarrhea), adenovirus, coronavirus
resistant to low pH
someone comes in w/respiratory infection w/assoc diarrhea think which virus?
coronavirus
viruses that can also transmit via: airborne (e.g.) and vomitus (e.g.)
airborne: norovirus
vomitus: astroviruses
rotavirus
syndrome, season, sero
acute GE in kids 4 are sero+
astrovirus
syndrome, season, sero
acute GE in kids
winter
75% of kids 3-4 are sero+
norovirus
syndrome, season, sero
acute GE in kids/adults
no seasonality
explosive outbreaks in schools/ships/institutions
adenovirus
syndrome, season, sero
infants/kids
no seasonality
sporadic outbreaks
coronavirus
syndrome, season, sero
children <1y
diarrhea assoc w/ respiratory infection
pathogenesis of diarrhea causers
1-3d incubation abrupt vomiting, diarrhea (watery; usually no blood), cramping headache, myalgia, low grade fever little inflammation/cell death shortening of microvilli toxins from rota/astro sx restricted to GI tract
mucus in stool
coronavirus
toxins of rotavirus/astrovirus
Rota: NS4 –> activates acyclase
Astro: capsid –> actin cytoskeleton opening cell/cell jxns
prevention/tx for diarrhea causing viruses
hygiene clean water/food NO ANTIVIRALS supportive for self-limiting HYDRATION DO NOT use agents that reduce peristalsis
rotavirus vaccine
human and bovine strains
no preservatives of thimerosal
incidence has dropped ever since
rotavirus vaccination for those after 12 weeks of age?
no b/c probably already exposed to the infection
croup
cough that sounds like child can’t breathe
how come we don’t have a vaccine for the common cold?
there’s too many of them
characteristics of respiratory viruses
3 sx of LRT infection?
all can cause sx in URT
several can cause LRT (bronchitis, croup, bronchopneumonia)
e.g. RSV, can start in URT, but then progress to LRT (see pt back if gets worse)
takehome on seasonal incidence?
can’t use this info to determine etiologic agent (peaks overlap)
influenza characteristic sx
fever (104); myalgia, fatigue, headache (notice not many resp sx)
abrupt sx after 1-2 day incub
fever/myalgia/malaise dry cough, sore throat, nasal congestion, rhinorrhea not prominent
systemic sx last 3-5d; resp sx last 3-4d longer and recovery of lung fxn can take weeks
influenze progression
risky groups?
dyspnea/cyanosis w/hypoxia
no lobar consolidation on CxR
kids/elderly/lung disease/heart disease/pregnant women
antivirals for influenza
amantidine/rimantidine: bind to M2 ion channel block viral entry into cells *(most strains are now resistant to this)
tamiflu/relenza: inhibit neuraminidase blocking release from cells (tamiflu is preferred currently of all)
secondary bacterial pneumonia
3 most common bugs?
most common in which pts?
classic flu w/improvement followed by fever, cough, sputum, consolidation on CxR
S. pneumonia, S. aureus, H. flu
elderly and lung disease
reassortment causes?
viruses that do this have what?
e.g.?
worldwide pandemics
only in viruses w/segmented genomes, occurs when two strains infect same cell
influenza
pandemic strains happen via what specific reassortment event?
hemagglutinin gene –> population has not seen new HA protein and thus is not protected
influenza reassortment detail
primarily a virus of which animal?
Hemagg and neuraminidase are major envelope proteins
waterfowl (birds)
pandemic reassortment –> new bird HA jumping into human strain
antigenic shift?
drift?
shift: reassortment that introduces a new gene sigmate into a circulating human flu strain
drift: pt MUT in current human flu strain that alters virulence; the reason for revaccination (along with protection not lasting that long)
avian strain v. human strain differences
avian: a2,3 sialic acid
human: a2,6 silica acid
pigs have both
influenza vaccine
killed virus v live strain (mist)
mist not for >50 or <5, pregnant women
protective for one year only
reduced efficacy in elderly
RSV
kids 6mo-1y (boys hospitalized) lethal in >65 and COPD 2-8d incubation, nasal cong, ST, fever (less than flu), cough, then dyspnea/wheezing IS infiltrates/hyperinflation on CxR bronch/pneumo/croup is rare OM/sinusitis can complicate
RSV therapy for whom?
ribivarin for hospitalized infants
steroid combo
RSV Ig in premature infants in first year
palivizumab-mAb against F protein in high risk kids
parainfluenza which types cause disease?
types 1 and 2 2-7d sometimes bronchitis, low grade fever 2-3d TYPES 1 and 3 --> croup TYPE 3 --> pneumo/bronchiolitis TYPE 4 --> rarely severe illness
PIV therapy
no antivirals/vaccine
support
hospitalization for croup
O2 and ventilation
SARS CoV
2-7d of mild URT sx
then fever, rigors, dry cough, dyspnea, malaise, headache, flu-like illness
27% have diarrhea
ARDS
rhinovirus
responsible for 2.3 colds/yr
smoking does not predispose, BUT results in more severe sx, no gender diffs
high 90% rate of symptomatic infxn
sneezing, runny nose, ST, cough, nasal congestion, headache, little/no fever
exacerbates asthma and bronchitis via EOS in lungs
OM/sinusitis complications
rhino tx
OTC antihistamines/decongestants, no antivirals, VitC, Zinc, Echinacea
adenovirus
most infected by age 10 latent in adenoids/tonsils boot camps infants: cough/ST kids: ST/tracheitis YA: more severe cough, fever, ST, runny nose adults: cold can progress to pneumonia
adenovirus tx
no antivirals
vaccine: encapsulated types swallowed to cause asymptomatic gut infxn to establish immunity (WILD TYPE strains used)
adeno pathogenesis (same in SARS, MERS, avian)
replicate in resp epith cells –> death/sloughing
debris clog airways
cytokines –> aches, fever, malaise (diff viruses –> diff cytokines –> diff sx)
inflammation of airways
edema and ARDS
alpha HHV
Beta HHV
gamma HHV
neurotrophic
lymphotropic
HSV-1/2, VZV
HCMV, HHV-6/7
EBV, HHV-8
alpha
beta and gamma
defining criteria of latency?
what happens during this period?
can’t detect infectious virus
virus replication shuts down but persists in genome of cell nucleus
2 outcomes of reactivation?
sx disease
asymptomatic shedding in the absence of any sx
sites of latency
HSV/VZV/HCMV/EBV/HHV
HSV 1/2: neurons VZV: neurons HCMV: monocytes EBV: B cells HHV 6/7: CD4 T HHV 8: maybe B's
only gene expressed during latency?
latency associate transcript
EBV latency proteins
for latent viruses in non-dividing cells: allows the viral genome to replicate along with cell and segregate into daughter host cells (LYMPHOTROPIC VIRUS)
what’s cool about EBNA 1?
can’t be processed and put on MHC-1 molecules
reactivation triggers?
stress UV light steroid hormones trauma to ganglia decr immune fxn
difference between simplex and zoster? what else is unique about zoster transmission?
zoster causes disseminated infection
can be spread by aerosol, otherwise close contact
exception to the rule of viral epidemiology (which is not positive in >50% of individuals?)
HHV-8
HSV-1/2 primary diseases (which are recurrent?*)
gingivostomatitis keratoconjunctivitis* cutaneous herpes (gladiatorum)* genital herpes* encephalitis* aseptic meningitis* neonatal herpes
herpes labialis* (only recurrent)
keratoconj: each reactivation immune resp causes more dmg to eye
how do we dx HSV?
PCR PCR on CSF for encephalitis culture w/IF can do Tzanck stain watch for neuro sx in encephalitis
jaundice, hepatosplenomegaly, microcephaly, petechial rash, mental retardation, chorioretinitis
congenital cytomegalic inclusion disease
sx more severe when infection occurs earlier in pregnancy
primary HCMV infections
HCMV reactivation infections
heterophile negative mono
hepatitis
cong cytomegalic inclusion disease
none in immunocompetent suppressed: donor organs can transmit BMT: IS pneumonia hepatitis in liver transplant pts kidney infection Retinitis in AIDS pts --> blindness
dx HCMV
saliva: owl eye cells
immunostain for antigens
PCR
no cultures - grows slowly
EBV primary infections
infectious mono (heterophile +: can detect this antigen for dx)
hepatitis
encephalitis (rare)
immunocompetent: no known reactivation disease
compromised: lymphoma and oral hairy leukoplakia (AIDS pts)
fever, ST, lymphadenopathy, tonsular exudate, palatal petechiae, heterophile antibodies
EBV mono
dx: monospot test or viral spec antigen
cancer in kids between 6-15y
jaw and long bones
assoc w/Malaria
EBV: Burkitt’s lymphoma
EBV cancers
Burkitt’s
Nasopharyngeal
mechanism of EBV and cancer
infects B cells and induces proliferation –> accum mutations in proto-oncogenes; Ig rearrangement –> chromosomal translocations (Cmyc) –> malignant transformation
EBV dx
triad of sx?
ST, fever, lymphadenopathy monospot test heterophile antibody + to sheep blood cells Downey T cells immunostaining no culture biopsies for solid tumors
roseola infantum caused by
HHV-6
self-limited febrile illness w/mild macular rash
only a problem if immunosuppressed
KHSV (HHV-8)
only if immunocompromised
Kaposi’s (AIDS and elderly) and Castleman’s
primary transmission: SEXUAL contact
KHSV dx?
Kaposi lesions: multifocal purple spots, PVR/immunostain/serology
antivirals: HSV1,2/VZV HCMV EBV HHV-6 HHV-8
trifluorthymidine/idoxuridine topical; acyclovir, valayclovir, famciclovir
foscarnet, ganciclovir
acyclovir, valacyclovir
ganciclovir
IFN, radiation/cytotoxics for cancer; restore immune system
mosquito-borne viruses
western/eastern equine encephalitis virus
st. louis encephalitis virus
california group enceph virus (LaCrosse in this group)
Colorado Tick Fever virus
mosquito-borne diseases
dengue: hemorrhagic (carribean/latin america)
venezuelan equine ecephalitis
yellow fever: hemorrhagic
chikungunya: arthritis (carribean)
animal borne viruses
diseases?
rabies, hanta, sin nombre
lassa fever: hemorrhagic (rodents)
ebola: hemorrhagic (bats)
ebola virus: presentation
fever, malaise, myalgia, headache –> pharyngitis, vomiting, diarrhea, mac-pap rash –> hmorrhagic diathesis and multiple organ failure –> death in 7-10d
urban transmission pattern
e.g.?
requires high titer to maintain cycle; prolonged viremia in vertebrate host
maintained in urban settings where humans are reservoir
e.g. Yellow Fever
Sylvan (wild) cycle
e.g. yellow fever cycle involves?
multiple reservoirs: birds, snakes, small mammals –> mosquito –> humans offshoot from cycle (i.e. get infected during a hike)
yellow fever: monkeys –> mosquito –> monkeys
animal-borne diseases
encephalitis (repl in CNS)
fever/hemorrhagic fever (repl in BV endothelium –> cytokines –> hypovolemic shock)
arthritis
yellow fever (repl in hepatocytes –> failure to produce clotting factors –> hemorrhage and vomiting blood
pulm hantavirus syndrome (repl in lungs –> ARDS –> edema
therapy for animal-born infections
no antivirals
can try ribivirin in life-threatening cases, or human IvIg
available vaccinations
yellow fever: live for travelers
rabies: killed for humans, live for animals (IvIg used in exposures)
horses for encephalitis
papillomaviruses: 2 types of disease
which four to remember? (are in current vaccine)
dsDNA, NON-enveloped, icosahedral
warts, cancer
HPV-6,11,16,18 –> cause genital warts
16,18 will much more frequently progress to cervical cancer
cancer w/papillomaV?
need cofactors –> additional mutations
90% of H&N cancers caused by?
HPV-16
does the DNA integrate in a normal papilloma infection?
no
What does E7 do?
binds Rb and removes E7 from cytoplasm –> cell continues to divide (when cell continues to divide triggers DNA damage response, mediated by p53)
BUT E6 eliminates p53 (removes cell brake)
papilloma dx
appearance PAP smear colposcopy acetowhite staining PCR
parapox virus
causes umbilicated papules on skin
if immunocompromised can spread and be mistaken for squamous cell carcinoma
molluscum contagiosum
polyomavirus (just need to know BK and JC)
JC virus –> progressive multifocal leukoencephalopathy
BK virus –> kidneys (can shed in urine), graft failure
both cause latent infxns
only cause above problems in IMMUNOCOMPROMISED pts
Parovirus B19 disease
Fifth Disease (slapped cheek)
Polyarthropy
Transient Aplastic crisis (pts w/increased erythropoiesis: replicates in hemapoetic precursor cells)
Hydrops Fetalis (congenital anemia)
Persisent anemia in immunocompromised pts