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Micro-Lect6: +RNA viruses

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For + RNA viruses what is the first step of the infectious cycle?
Delivery of their genomic RNA to the cellular ribosomes for direct translation.
What do +RNA viruses need to be infectious?
Only their DNA, no proteins needed.
What does subgenomic RNA mean?
Genomic RNA directs the synthesis of a precursor for nonstructural proteins, esp. viral RNA-dep. RNA Pol and modifying proteins.
Allows these to regulate the production of viral proteins at dissimlar levels.
Which +RNA viruses have subgenomic DNA processing?
Togavirus (alphavirus) and coronaviruses
What is tropism?
The ability of a virus to enter a cell or organ/system
What are zoonoses?
Infectious disease transmissable between vertebrate animals and humans
What are arboviruses?
Mixed set of RNA viruses tat are transmitted by insects.
What are the vectors of arboviruses?
ticks, lice, midges, mosquito
What is the sylvatic cycle?
"jungle" cycle without human involvement
What are the +RNA arboviruses?
WEE, EEE, VEE, St. Louis/west nile encephalitis, dengue/yellow fever, russian spring-summer encephalitis. All are from the mosquito except the russian
What is the structure of the Flaviviruses?
enveloped icosahedral nucleocapsid; small diameter 37-50, one surface glyoprotein with a second membrane protein.
How is the polyprotein processed in Flaviviruses?
Autocatlytic activity of viral protease (PRO) liberates structural proteins from nonstructuals (polymerase and accessory proteins)
How are flaviviruses spread?
All by insects x HepC
What diseases do flaviviruses cause?
Yellow fever
Dengue
St Louis/Japenese B/West Nile encephalitis
HepC
Russian Spring-Summer encephalitis
Powassan encephalitis
What are the clinical features of Yellow Fever?
*acute febrile illness
*jaundice, hemorrhage, and proteinuria
*initial growth of virus in draining lymph nodes from bite
*viremia spreads to many organs
What is the transmission scheme for yellow fever?
Vector is mosquito (aedes) and the monkeys are the resevoir
What is the epid. of yellow fever?
endemic to central america, south america, and africa
What is the treatment strategy for yellow fever?
vaccine with a live attenuated virus
What is the clinical presentation of Dengue?
4 serotypes; immunity to one subtype if reinfect same, worse dz-->dengue hemorrhagic fever if another serotype

*joint, muscle, head, back pain for 5-6 days; high biphasic fever
What is the clinical presentation of Dengue hemorrhagic fever?
same onset as DF with hepatomegaly, hemorrhagic manifestations and shock.

10% mortality
What is the transmission scheme for dengue?
mosquito=aedes
humans in the urban cycle can propagate cycle
What is the epid. of dengue?
now widerspread: india, se asia, china, japan, south america, africa and middle east.
What is the clinical presentation of the West Nile encephalitis group?
Range of symptoms among pts
*mild infx: fever and ha
*acute encephalitis: Marked onset, HA, high fever, stiff neck, stupor, disorientation, tremor, coma can progress to paralysis seizure and death
What is the least severe in the west nile encephalitis group?
St. Louis
What is the transmission scheme for WN?
generally Culex mosquito, but ranges with habitat
What is epid. of WN?
Mostly SE asia
What is the clinical presentation of HepC?
*Jaundice and hepatitis, incubation 8-10wks
*high incidence of cirrhosis and CA after 10-20 yrs
*high rate of chronic infx
What is the transmission scheme for HepC?
Parentral transmission;infected blood, mother-child, and sexual
Blood supply screened for prevention.
HUMAN ONLY!
What is the epid. HepC
10% africa
world 3%
What is the structure of the togavirus?
*enveloped virus studded with spike-like trimers with heterodimers of surface glycoproteins E1 and E2
*Icosahedral
*45-75
*structural genes are at the 5'end=subgenomic RNA expression
Name the highlights of togavirus replication>
1. Temporal regulation of protein expression
2. Acidifcation in vesicle leads to membran fusion
3.Subgenomic RNAs imperative for viral replication
4. Virions bud out of cell plasma embrane
What are the alphaviruses?
Subset of togaviruses that infect humans
How do alphaviruses cause human dz?
inhibit host cell protein, RNA, DNA synthesis through their nonstructural proteins
Structural proteins promote cytolysis
What are the diseases of the Alphaviruses?
Rubella
Eastern Equine Encephalitis
Western Equine Encephalitis
Venezuelan equine encephalitis
Chikungunya
sindbis virus
semliki forest virus
What is the clinical aspects of rubella?
*acute febrile illness with rash and LAD in kids for 3 days.
*Causes problems in pregnancy with Congenital RUbella syndrome
*Incubation 2-3wks, then 3 day rash
What is the treatment for rubella?
Vaccine-live attenuated virus
What is the transmission of rubella?
respiratory
What is the clinical presentation of Congenital rubella syndrome?
maternal infection in feturs. growth of cells effected. Inc. risk of abnormalisties earlyier in the pregn.

*Congenital heart dz, blindness/cataracts, enlarged liver and spleen, MR
How do you dx CRS?
by IGM for rubella virus in the infant
What are the clinical aspects of Eastern equine encephalitis (EEE)?
range: mild flu-like to frank encephalitis, coma, and death
What is the Path of EEE?
virus replication in the host and can have neurologic sequelea, 35% fatal
What is the transmission of EEE?
Bird-mosquito-bird cycle NL then gets to humans from bird
What is the epidemiology of EEE?
low 5cases/yr in US
What is the treatment for EEE?
Killed vaccine available
What is the clinical pix of WEE?
same as EEE, mild to severe neurologic deficits in survivors
What is the epid. of WEE?
19 cases/yr in the US
from mosquitos
What is the treatment for WEE?
Killed vaccine available
What is VEE
same as EEE and WEE x in venezuela
What is Chikungunya>?
febrile illness in asia and africa from mosquito
What is the structure of coronaviruses?
large, enveloped, +RNA viruses, with a helical nucleocapsid,
single strand, non-segmented RNA caoted with N-protein.
27-33=largest genome of RNA viruses
What are the major viral proteins of cornoaviruses?
3 glycoproteins:
E1, E2, and Hemagglutinin (HA) that give halo apperance to the virus
WHat is uniquie about the RNA of the coronavirus?
it has a cap on 5' end and a poly A tail on the 3' end

subgenomic expression
Highlights of the Replication of Coronaviruses?
1. each subgenomic RNA has an identical leader sequence/
2. leader originates from 5' end, then is "slipped" to gene ORF where gene trxn starts
3. Complex regulation by "nested" mRNAs, each responsible for expression of seperate genes at distinct times
4. Coronas assemble and bud into the golgi, get envelope from golgi lipids and released by endocytosis
what is the pathogenesis of Corona?
Only the coronavirus of the cornaviridae family affects humans and there is now 3 groups: 1=strains like 229E 2=strains like OC43 3=SARS
what is the transmission scheme for cornoaviruses?
respiratory
infx begins when the virus recognizes a cell surface receptor
What do the different classes of corona viruses recognize?
HCo-V 229E= aminopeptidase N
HCo-V OC43= Sialic acid
HCo-V SARS= ACE2 and DC-SIGNR(dendritic cell specific intracellular adhesion molecule grabbing non-integrin)
What diseases do coronaviruses cause?
1.Common cold
2. SARS
3
What is the clinical picture of common cold?
* Major cause in winter months
* highly variable year to yr
* spread by respiratory secretions
**Incubation 2-5days, sx 5-7d
Immunity directed to E2
What is the clinical picture of SARS?
*fever, dyspnea, lymphopenia, lower respriatroy tract infx
Also: GI infx/diarrhea--active viral replication in small and large intestinces//
*dec. platlet counts, prolong coag, mild Inc. liver enzy

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