virology 2 Flashcards
describe the measles and mumps in terms of the structure of the virus and their nucleic acid content
paramyxovirusesRNAsingle strandednegative senseenvelopedhelical
do paramyxoviruses have to carry RNA polymerase?
yes
are measles and mumps capable of radical antigenic shifts?
no- paramyxoviruses only contain one strand of RNA
how does the type of infection dictate the incubation period and subsequent immunity for measles and mumps?
they travel through the blood as viremia and cause systemic infections. thus:1 incubation time is longer2 IgG provides life long immunity
how many serotypes of mumps are there?
1
how many other animals act as resevoirs for mumps?
just humans
what is the normal incubation period for mumps?
3 weeks
what are the symptoms of mumps?
after 3 weeks, prodromal symptoms will developfever, malaise, anorexiafollowed shortly by asymmetrical parotiditis and potentially orchitis post puberty. parotiditis is the presenting symptom.aspetic meningitis is also common
describe transmission of mumps
occurs usually via respiratory exposure to saliva droplets containing virionviremia spread from the parotids to the salivary glands, where virions produced there enter the mouth and spread via coughs and sneezes
describe antiviral therapy for mumps
none
describe the vaccine used for mumps
live-attenuatedparted of the MMR vaccine given twice
explain the occurrence of 3 year cycles of epidemics for measles
measles is the most contagious disease known. an outbreak would result in herd immunity, but as years go by and new people are born, the proportion of immune people decreases to a critical point where herd immunity is no longer effective, causing a new epidemic
describe measles transmissoin
transmitted through respiratory droplets (coughs/sneezes) and infects respiratory tract.it multiplies in the lymph and respiratory epithelium
describe measles symptoms
prodromal symptoms occur first:fever, cold-like symptoms, runny nose, red eyes, coughing, sneezing, photophobiafollowed by Koplik spots (bright red lesions w white central spot inside mouth)- predicts measles rashrash begins after 14 days. maculopapular erythematous rash generated at least partially by immune system
describe measles virus excretion
excreted from respiratory tract and in tears and urine in the days before and after rash
measles incubation period
14 days
measles complications
- pneumonia2. otitis media3. acute encephalitisdeath in 1/1000complications more common in kids under 5, people over 20, and immunocompromisedgiant cell pneumonia- sometimes pneumonia results w/o measles rash d/t suppression of cell mediated immunity
measles treatment
nonetreatment with vitamin A in developing countries has helped reduce mortality- death often occurs w/ measles and malnutrition
does mumps or measles cause syncitia
measles
describe what measles does to cell mediated immunity
suppresses it, causes anergy
how many serotypes of measles are there?
1
how many animals act as a resevoir for measles?
just humans
describe measles immunization
live attenuatedgiven twice in MMRlife long protection
“slow viruses”
- long incubation period (years)2. relentless course leading to death3. genetic predisposition4. re-emerge from latency b/c of immune suppressionexamples: HIV, JC, BK neuropathy
JC virus
papovaviruscauses progressive multifocal leukoencephalopathy (PML)PML is a progressive demyelinating disease of the brain (affects oligodendroglia) w/o inflammationoccurs w/ immunosuppressionprogression includes blindness, dementia, and death
SSPE
subacute sclerosing panencephalitisonset of intellectual deterioration, psychological disturbance, blindness and terminal paralysisassociated w/ measles- - high Ab to measles- CNS contains measle antigendistinct inclusion bodies. relation to measles unclear. does occur after vaccination (one in a million)
prion characteristics
1 long incubation period2. slow relentless course to death3 confined to CNS4 produce spongiform encephalopathy5. genetic predisposition
what are prions?
theorized to be infectious proteins w/o nucleic acid
what are the 5 spongiform encephalopathies caused by prions?
KURUCDJ Cretzfeld-Jacob diseasevariant CDJ mad cowGSS- gerstmann straussler scheinker syndromefatal familial insomnia
scarpie
chronic progressive CNS disorder in adult sheepgenetic predisposition indicatedincubation period of less than a yearprion disease- no nucleic acids
KURU
progressive degenerative disorder of the CNS, especially the cerebellumlimited to small tribe in new gunieano environmental factors- partially geneticcould be transmitted to apes by eating the human brains
CDJ
most common human prionmost are the result of a mutation, w/ obvious cause. risk increases w/ agesome reported cases were iatrogenic- caused by physicians using contaminated surgical equipmentsome variants are linked to families fCDJsome are sporadic sCDJ
mad cow
variant CDJcaused an epidemic in great britain as a result of using brains/bone marrow of cows to feed other cows, which became infected, and when consumed, infected other people
describe the structure of a herpes virus
DNA, double strand, enveloped, icos
describe the herpes life cycle
adsorption and fusion w/ hostnucleocapsid releases viral DNA into nucleusDNA becomes circularmRNA, viral protein synthesis inside nucleusprogeny nucleocapsids assemble in nucleus causing inclusion bodiesviral glycoproteins are inserted into membrane (can cause syncitia)progeny bud out from membrane**needs nucleus
describe how herpes is eliminated from the body
herpes is not eliminated from the body, even upon asymptomatic recovery. instead, herpes becomes latent. even in asymptomatic latency, pts may sporadically create infectious virions
describe the subclassifications of herpes virus and some examples
alphaherpesvirus- HSV1- wide host range, latency in neuronsbetaherpesvirus- CMV- narrow host range, latency in monocytesgammaherpesvirus- EBV- narrow host range, latency in B lymphocytes
latency
all herpes viruses can become latent:non destructivelifelongpersistence of viral genome in non infectious statepotential to be reactivated
is latency active or static?
active-creating gene products that prevent apoptosis, but opens the virus to immune recognitionalso have asymptomatic shedding
why could herpes be good for you?
chronic stimulation of immunity by non-lethal pathogens could be beneficial
HSV1- primary and recurrent infection mechanisms
“cold sores”primary infection often subclinical and most commonly causes stomatitis virions produced at the site of initial infection travel up sensory neurons to nearest ganglion (often trigeminal ganglia) and establish latent infectionrecurrent infection occurs when viral multiplication resumes and virions are tranported down axons to cutaneous site of primary infection- results in cold sores
what % of the population has HSV1?
> 80%
what is the incubation period for HSV 1
1-2 weeks
what factors can aggravate latency, causing a recurrent infection?
UV lightfeveremotion
HSV1 vaccine
none
HSV2
“genital herpes”primary infection of genital mucosa, virus follows sensory neurons back to ganglia and establishes latency (sacral ganglia)
HSV2 incubation period
1-2 weeks
what % of the population has HSV2?
20%
describe the complications of HSV2 and perinatal infection
virions released by vaginal secretions can cause systemic disease in newborns ~6 days after birthdisease is often fatal, with destruction of liver and adrenalmost dangerous scenario is when mother has just gotten primary infection and has no AbHSV2 shedding before deliver is indication for C-section
HSV1 and 2 also cause what in addition to skin lesions
encephalitisocular disease
herpes simplex encephalitis
most common cause of sporadic encephalitis- usually HSV1causes high fever, confusion, lymphocytes in CSF, lesions on MRIoften death w/o early recognition
treatment for herpes simplex encephalitis
acyclovir
herpes simplex keratitis
herpes simplex infection of eyeunilateral red eyecan cause blindness if untreated
does herpes simplex cross placenta
no
how do you diagnose herpes simplex?
isolation and cultureELISADNA PCR of CSFserology (IgM in primary infection)
HSV2 vaccine
none
what are the treatments for herpes simplex
acyclovir- gold standardherpes thymidine kinase will phosphorylate ACV, which can then be subsequently be phosphorylated by host and incorporated into DNA, which halts synthesis and causes death in infected cells
varicella zoster virus
chickenpox/shinglesprimary infection causes chickenpox- infection through respiratory tract- causes viremia. then spreads to the skin andcauses small itchy vesicles (rash) and fever. then travels retrograde to sensory neuronsoften fatal to immunosuppressed
varicella zoster virus transmission
aerosolspread from mucosa in skin lesions to the respiratory tract. vesicles in respiratory tract may also rupture and spread disease
treatment for varicella zoster virus
can get IgG- VZIG or acyclovir
congenital varicella syndrome
fetal infection from a pregnant mothercauses limb atrophy and scarring of the skin
zoster
shingles- more common w/ agereactivation in a sensory ganglia that results in pain distributed along a specific dermatome, followed by lesionscan be followed by post-herpetic neuralgia- residual painmore
zoster treatment
acyclovir
vaccinations to varicella zoster virus
vaccines to both varicella (live attenuated, requires boosting) and zoster
CMV
causes enlarged cells w/ “owl eye” inclusion bodiescauses retinits, colitis, heterophile negative monoleading cause of congenital abnormalities- from infection in 1st trimester- can go through placenta
CMV immune evasion
has 6 genes to evade T cell activation via disrupting antigen presentation
CMV transmission
blood/ bodily secretions (urine)
CMV infects what
epithelia- moves to ganglia- infects monocytes
easiest way to test for CMV in neonates
CMV in urine
CMV vaccine
none
CMV treatment
ganciclovir or foscarnet
CMV findings in newborns
retinal inflammationjaundicelarge spleen and liverlow weightmineral deposits in brainrashseizuressmall headretardationdeafness
EBV
causes heterophile positive mono and cancersubclinical infections in kids, but more prevalent post puberty1st symptom is sore throatalso: fever, sore throat, lethargy
EBV transmission
salvia or oral contactseen in college aged peopleinfects mucosal epithelia before spreading to B lymphocytes. can become latent w/ these b lymphocytesseen in people post puberty
EBV vaccine
none
EBV incubation period
2-4 weeks
% of population with EBV
90%
describe the immune response to EBV
CTLs develop to clear infected B cells, causing abnormal cellular phenotype in blooddevelop Abs that cross react w/ sheep RBCs, creating a diagnostic test
diagnostic tests for EBV
look for CTLs or test for agglutination with sheep RBCsIg to viral capsid
EBV treatment
no treatment
HHV6
most prevalent herpes virus > 90%genome can integrate w/ human genome and becomes heritablecauses: roseola infantum and exanthm subitum (rashes) w/ high fever
HHV7
causes infections but w/o symptoms
HHV8
Kaposis Herpesvirusnot seen in 1980s b/c of AIDS.common in sexually transmitted HIVforms spindle epidermal cellsalso in GI and lungsrarely seen in US b/c of antivirals tumor virus
HHV8 treatments or vaccines
none
B virus
infection of rhesus macaques (benign in monkeys, not in humans)very rare- seen in people who work in animal facilitiescaueses encephalitis, serious neurological squelae, and death
B virus treatment
acyclovir
triflurodine
useful in treating keratitis simplex infections causes nucleotide form of triflurodine to be incorporated into DNA and to halt DNA synthesis.cells in cornea replicate slowly enough that only infected cells will die off
adenine arabinoside
analogue of deoxyadenosine that gets phosphorylated by host enzymes an incorporated into DNA, halting DNA synthesis
foscarnet
inhibits DNA polymerase of herpes virus selectivelyalternative to ganciclovir in CMV
what does transformation mean?
cell can grow indefinitely and growth cannot be arrested. it requires less serum, does not exhibit contact inhibition, and is anchorage independentis “tumorigenic”
what is the mechanism by which viruses cause tumors
two ways:RNA viruses will introduce, upregulate, or mutate proto-oncogenesDNA viruses will degrade or sequester tumor suppressor genes
how can you detect oncogenic viruses in tumors?
- take cell free extract and inject into animal model/cells to see if tumors form2 use fluorescent Abs, western blot, ELISA, etc. to look for viral proteins3 use PCR, northern blotting, southern blotting, etc. to look for nucleic acids
describe how the morphology of cancer cells differs from regular cells in vitro
regular cells grow flat, in an ordered waycancer cells grow rounded, disordered
describe the biochemical differences between cancer cells and regular cells in vitro
cancer cells have higher rates of glycolysis and glucose transport. they have lots of proteinases, but reduced fibronectin and actin
papovirus characteristics
DNA, double stranded (circular), naked, icosahedralproduces 10 genes, all of which are essential for tumor growth
what are some examples of papoviruses?
papilloma virus- infects humanspolyoma virus- rodentsSV40- monkeys
describe papovirus replication. how is this related to its tumorgenic properties?
replication divided into early and late stagesearly replication involves host RNA polymerase transcribing the T-antigenT-antigen binds the origin of replication. host DNA poly recognizes and binds the T-antigen, beginning replication.following replication, late replication starts and transcribe the viral capsidsviral capsids self assemble and cause lytic burst of cellin addition to binding origin of replication, T antigen also binds and inactivates p53 and Rb tumor suppressors
what cells does HPV infect?
epithelial cells- no viremia- grows locally,
what does HPV cause
warts and condylomas (genital warts)6 and 1 1- most common cause of condylomas16 and 18- cause cervical cancer
which strands of HPV cause cervical cancer? how?
16 and 18- they have oncogenes E6 and E7, which bind p53 and Rb respectively, targeting them for destruction and thus inactivating them
what is another large cofactor for developing cervical cancer when infected w/ HPV
cigarette smoking
describe the gardisil vaccine
protects against 6, 11, 16, and 18dead virusgiven in 3 doses over 6 months to people 9-26
describe the cervarix vaccine
protects against 6 and 11 onlydead virus3 doses over 6 months
do adenoviruses cause cancer in humans?
no- cause cancer in rats
how do adenoviruses cause cancer?
two important proteins: E1A binds and inactivates Rb, p300, and CBPalso binds to transcription factors to initiate S phaseE1B upregulates E1A
describe herpes virus characteristics?
DNA, double stranded, enveloped, icosahedral
what herpes viruses cause cancer?
EBV and Kaposis sarcoma virus (HHV8)
EBV cancer
causes burkitts lymphoma- a B cell lymphomacauses tumors in jaw, heart, abdomen, but does respond to chemo(can also cause nasopharyngeal carcinoma in Asia but mechanisms not understood)
how does EBV cause cancer
extrachromosomal EBV genomes always found in b-cellsinfection is latent, and integration is not required for transformationtranslocation puts c-myc proto-oncogen under transcriptional control of an Ig- over expressionT-cell normally controls these B-cell except under immunosuppression or in immunocompromised individuals
what are two important EBV genes that cause transformation
EBNA-2 transcriptional activatorLMP-1- CD40 analogoue
where is Burkitts lymphoma found
equitorial africa- coincidence w/ AIDS and malaria
Kapsois Sarcoma herpes virus cancer mechanisms
Kapsois sarcoma most common cancer w/ AIDS, but is uncommon w/o immunosuppresiontumors present w/ multiple, pigmented, high vascular skin nodules. tumor cells express VGEFviral genes: GPCR (VGEF) and LANA (cell growth)
retrovirus characteristics
RNA, single stranded, positive sense, enveloped, helical
essential retrovirus genes
gag- nucleocapsid proteinspol- reverse transcriptase and integraseenv- envelop glycolipids
retrovirus classification
divided into oncoviruses and lentiviruses (no cancer)oncoviruses have 3 classifications:transducing- have captured an onco-gene and insert it directly. transformation is short. usually cannot replicatenon-transducing- don’t have an oncogene, instead cellular oncogene is activated by provirus. replication intact. intermediate transformation timenon-transducing, long latency- long transformation. viral protein influencing transcription
provirus
retroviruses are positive sense single strande RNARNA transcriptase converts the RNA into double stranded DNA and integrates it into host genome. this serves to make mRNA for future progeny and is called a provirus
long tandem repeats
Reverse transcriptase adds regulatory elements to the ends of the DNA it creates
describe retrovirus replication
enters cytoplasm. reverse transcriptase begins at primer tRNA, creating a RNA-DNA hybrid. RNase H degrades the viral RNA, and reverse transcriptase finishes the DNA.DNA is longer because of LTRs. it moves into the nucleus and integrates, becoming a provirushost DNA polymerase and replication machinary create and translate mRNA and viral proteins, eventually creating entire viral genome copies that can then leave
RSV
rous sarcoma virus- transducing virus- transforms w/in 24 hours of introduction to chickenencodes src oncogene (tyrosine kinase)
what types of proteins make good protooncogenes
growth factorsgrowth factor receptorskinasesG proteinsproteins that regulate transcription and regulation
how do acute transforming viruses replicate?
they cannot replicate themselves because one of their 3 essential genes has been replaced with an oncogene. if they are to grow, they need a helper retrovirus to coinfect the cell and provide the missing proteins
what are the human carcinogenic retroviruses?
HTLV 1 and 2. they do not have oncogenes
how is HTLV transmitted
blood, semen, perinatal (bodily fluid)
where does HTLV infect?
mucous membranes- viremia- t-lymphocytes
what does HTLV 1 cause?
adult t cell leukemia (.1% of infected, everyone else is usually asymptomatic. takes years)
hepatitis B cancer
5% of hep b cases become chronic. 5% of those cases get liver cancer.cause unknown, but hep viral genome integrates w/ host.theories: inserts near proto-oncogenehas an oncogenedestruction and redevelopment of liver provides opportunities for errors
what are the differences in how hepatitis b and retroviruses use reverse transcriptase
retrovirus is an RNA virus, and uses it to create DNA provirus that can integrate into the nucleushep B is a DNA virus. it creates mRNA copies of itself, which are then put into the capsid, and reverse transcriptase then generate the proper DNA format at the end of the lifecycle
hep C cancer
20% of people with chronic hep C develop cancer. there is no oncogene and integration does not occur.
arbovirus characteristics
RNA, single stranded, plus stranded, enveloped, icosahedral
how are arboviruses transmitted?
via blood sucking arthropod hosts (mosquitos and ticks)
difference between intrinsic incubation and extrinsic incubation
intrinsic- incubation in humans- usually 1 weekextrinsic- inside the arthropod, virus is not infectious until 14 days. arthropod is then infected for life
in the USA, what is the only serious disease concern stemming from arboviruses?
encephalitis
can you get human to human transmission?
not really- not unless blood transfusions
describe the progression of arboviral encephalitis
incubation is 1 weekviremia occurs quickly. virus multiplies in vascular endothelium.causes febrile malaise followed by encephalitis, paralysiss, coma and death
what is the treatment for arboviral encephalitis?
none
describe eastern equine encephalitis (EEE) and western equine encephalitis
togavirus- RNA, ss, +, enveloped, icosassociated w/ focal outbreaks in summer months, usually near swamps or after rainy seasonshorses and humans are dead-end hosts- usually die before can infect mosquitosinstead, the virus is maintained in nature via transmissions between mosquitos and birds, neither of which develop symptoms
west nile virus
flavivirusRNA, ss, +, enveloped, icosmost common cause of arbovirus in US. imported from egypt recently, now in every state.maintained by bird-mosquito cycles. humans are dead end hosts. most fatal cases are in elderly
st louis encephalitis
flavivirusRNA, ss, +, enveloped, icosantigenically related to west nile, native to US. most fatal cases in elderly
dengue fever
arbovirus- flavivirusRNA, ss, +, enveloped, icos4 typesincubation period 1 week- humans are not dead-end hostsfever, severe headache, muscle and joint pains, rash
what are the symptoms of dengue fever
fever, severe headache, muscle and joint pains, rash
dengue hemorrhagic fever
more severe form, notable for hemorrhage, vomiting blood, and shockcaused w/ sequential infections of cross reacting dengue fevers result in excessive inflammation and vascular permeability
yellow fever
arbovirus- flavivirusRNA, ss, +, enveloped, icoscauses fever, nausea, jaundice, hemorrhageextensive multiplication in liver, spleen, and kidneys
how are yellow fever and dengue transmitted?
human-mosquito-human-mosquitoin the jungle, monkeys can also become infected w/ yellow fever and serve as a resevoir from which we can get infected
yellow fever vaccine
live attenuated
zika
arbovirus, flavivirusRNA, ss, +, enveloped, icoscauses a mild form of dengue, may cause microcephaly
what defenses does a fetus have against viral infection?
placentamaternal IgGfetal IgMinterferoncell mediated immunity?
parvovirus B-19 characteristics
DNA, single stranded, unenveloped, icos
how is parvovirus transmitted?
through respiratory tract or transplacental
what is the parvovirus incubation period?
14 days
what are the symptoms of parvovirus?
asymptomatic orfever, malaise, erythema infectiosum (slapped cheek), transient athritis
where does parvovirus replicate?
RBC precursors- causes lack of new RBCs for a week, which is tolerated fine normallytransient aplasic crisis- person w/ anemia infected with parvovirus has severe deficit in O2 carrying ability
hydrops fetalis
transplacental infection during first or second trimester can cause death w/ severe swelling
rubella characteristics
togavirus- NOT ARBOVIRUSRNA, ss, +, enveloped, icos
rubella incubation
18 days
rubella transmission
respiratory aersols
rubella multiplication
respiratory epithelium followed by viremia
rubella symptoms
skin rash (3 days), fever, lymphadenopathy, transient arthritis
rubella vaccine
live attenuatedpurpose is to prevent congenital rubella
congenital rubella syndrome
virus crossing the placenta in the first trimester can have a variety of effects including:cataractsheart defectsdeafnessretardationspontaneous abortion
describe poxvirus characteristics
DNA, double stranded, asymmetric capsid, both enveloped and uneveloped
what characteristics of poxvirus distinguish it from other viruses?
it has an asymmetrical capsid and can be infectious enveloped or unenveloped
does the virion require host RNA polymerases?
no, it carries its own.poxviruses are the only viruses that carry a DNA dependent RNA polymerase with them
where do poxviruses form their inclusion bodies?
cytoplasm
what do inclusion bodies indicate
they indicate sites of virion or nucleocapsid assembly.can be used to help distinguish viruses
molluscum contagiosum
poxvirus transmitted by intimate cutaneous contactcauses white skin papules- bumps on the skinmuch worse in immunosuppressedresolves on its own w/ t-cell immunityharmless
how is molluscum contagiosum transmitted?
intimate cutaneous contact
how long is the incubation period for molluscum contagiosum?
2-8 weeks
why can it be difficult to diagnose molluscum contagiosum
grows poorly in culture
smallpox characteristics
DNA, double stranded, asymmetric, both enveloped and nonenveloped
smallpox transmission
respiratory
describe smallpox infection
infects respiratory mucosa and lymph, establishes viremia that attacks lungs, liver, spleensecond viremia infects skin
what is the clinical presentation of smallpox
papules, vesicles, pustules.lesions in oral mucosa are the main source of new infection
smallpox virus vaccine
live- vaccinia virus
how many serotypes of smallpox are there?
1
how many other animals act as resevoirs for smallpox?
0- just humans
complications of smallpox vaccinations
encephalitisvaccinia necrosum- spreading necrosis at site of infection d/t t-cell immunityeczema vaccinatum- pread of lesion in pre-exisitng eczemageneralized vaccinia- spread of lesions in the absence of eczemaheart infection
when is the smallpox vaccination useful?
prior to infection or w/in 4 days of infection
what other treatments work for small pox
passive immunization w/ IgG
rhabdovirus characteristics
RNA, single stranded, minus strand, enveloped, helicalrabies
rabies transmission
bite from infected animal
rabies infection
no viremia- tropism for nervous systemreplicates into salivary glands
incubation period of rabies
week to months
rabies prognosis untreated?
human and canines- fatal
rabies symptoms
fever, anorexiaLater: hydrophobia (d/t swallowing pain), paralysis, coma, death
rabies diagnosis
negri bodies- cytoplasmic inclusions in nerve cellsuses fluorescent Abs to confirm
where are herpes inclusion bodies?
nucleus
rabies vaccine
killed vaccinecan be given any time during the incubation period, but once CNS symptoms begin, will not stop death
rabies treatment
combination of passive and activeIgG given to delay symptoms and then killed vaccine used to activate active immunityused in all cases of unknown bites or prophylactically w/ vets
how does transmission usually occur in the US?
bites from wild animals’ (bats, foxes, racoons, etc.)dogs are not a big source (except near mexican border) b/c of vaccination requirements
