4.37 Flashcards by sophie rosen

Viral Gastroenteritis (3)

– Inflammation of stomach or intestines
– important disease of infants and children
– leading cause of childhood death in developing
countries

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etiologic agent: Rotavirus, Group A
genome:
medical significance:

segmented dsRNA

major cause of diarrhea in children 6-24 months

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etiologic agent: rotavirus, Groups B & C

genome:

segmented dsRNA

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etiologic agent: norovirus
genome:
medical significance:

(+) ssRNA

major cause of diarrhea outbreaks in children and adults

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etiologic agent: sapovirus

genome:

(+) ssRNA

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etiologic agent: enteric adenovirus

genome:

linear dsDNA

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etiologic agent: astrovirus

genome:

(+) ssRNA

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etiologic agent: aichi virus

genome:

(+) ssRNA

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~–% of diarrhea cases still have unknown etiology

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1st virus identified from stool samples by electron microscopic examination (1972)

Norwalk

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Rotaviruses are members of the — family

Reovirus

Respiratory Enteric Orphan viruses

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Rotaviruses (4)

Nonenveloped
Inner and outer capsids
RNA-dependent RNA polymerase
Genome = 11 segments of double-stranded RNA (dsRNA)

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— of infected cells

Lysis

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Rotaviruses
characteristics (3)

potentially fatal dehydration
fecal-oral transmission
watery-diarrhea

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Rotaviruses

fecal-oral transmission

acid stability conferred by double capsid structure
up to 1012 virus particles per ml stool
as few as 10 virus particles can cause infection

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Rotaviruses

watery-diarrhea

virus produces an enterotoxin
binds integrins; signaling results secretion of chloride and water
infected gut epithelial cells destroyed & replaced by immature epithelial
cells (reduced uptake of ions, water; less absorption of foods molecules
(carbs))

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Rotaviruses

detection

Group A most common type in United States

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Rotaviruses

Rotavirus vaccine for infants (>75% effective)

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Noroviruses
characteristics (3)

positive strand RNA genome
~7,500 bases in length
Naked capsid virions

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Noroviruses

replication

Replication similar to
picornaviruses (poliovirus)
except 2nd phase of
translation involves
subgenomic RNAs (like
coronaviruses).
- Has a 5VPg protein on RNA
(like picornaviruses)

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Adenovirus 
characteristics (3)

linear double-stranded DNA genome
nonenveloped
icosahedral capsid

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adenovirus
•viral nucleoprotein complex
enter

cell nucleus

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Adenovirus gene expression
— regulation
pre-early, early, late genes

temporal

—- regulators
produced during one phase
act to promote transcription
of genes of subsequent phase

transcriptional

Adenovirus DNA replication

only one of the 2 DNA strands is copied at each replication fork no discontinuous replication (lagging strand replication) priming is by a viral protein, pTP (preterminal protein)

Adenovirus infections | widespread: ---% of all viral infections

5-10

Adenovirus infections | symptoms

usual symptoms resemble common cold

Adenovirus infections | vaccine

Vaccine (live virus) given to new military recruits | targets serotypes 4 and 7

disease: acute respiratory disease (ARD) | adenovirus serotypes: (2)

4, 7

adenovirus | Mechanisms for evasion of host defense

``` block MHC class I mRNA production block transport of MHC class I proteins to the cell surface viral E3gp19K protein does this (see next slide) results in block of killing by cytotoxic T cells ```

Adenovirus drives the host cell into cell division (3)

necessary for adenovirus to replicate (needs cellular S phase factors) Adenovirus E1a and E1b proteins interfere with cell division controllers Viral infection can potentially drive a cell toward a cancerous state

Adenovirus E1a and E1b proteins interfere with cell division controllers E1b sequesters --- E1a sequesters ---

p53 | Rb (retinoblastoma protein)

Example: DNA damage during G1

P53 recognizes DNA damage and activates P21 (p53 recognizes certain types of DNA mismatches) P21 binds and inactivates the cyclin-CDK complex which has already begun to be produced in response to different signals DNA repaired, p53 decreases, P21 no longer blocks cyclin-CDK, cell cycle progression

P53 act as a checkpoint controller to stop

cell-cycle progression

Inactivation of p53 by adenovirus E1b protein | prevents

activation of p21 (and Bax)

Adenovirus E1a protein binding to Rb complex | prevents

Rb from negatively regulating E2f

``` Human papillomaviruses (HPVs) characteristics (2) ```

nonenveloped viral particles | genome is a ds circular molecule

Human papilloma viruses (HPV) | At least --- different HPV types

100

Human papilloma viruses (HPV) | --- HPV or --- HPV

cutaneous | mucosal

Infection process | --- month process (usually)

3-4

Infection process | 3-4 month process (usually)

HPV accesses basal layer through breaks in skin Viral early genes stimulate cell growth (which facilitates viral replication) HPV reproduction coordinated with development of keratinocytes (Keratinocytes = nondividing, physical barrier; anuclear) As cells move through skin layers HPV gene expression and DNA replication begins (uses cellular DNA polymerase) Late proteins (capsid proteins) only made in differentiated layers Assembly occurs in nucleus during keratinocyte development Nuclear remnant with viral particles shed at skin surface. HPVs are not lytic.

Koilocytes -

enlarged keratinocytes with clear halos | around enlarged nuclei - characteristic of HPV infection

HPV spread by skin-to-skin contact: | 3

``` breaks in skin -for example, scratching mucous membranes - more susceptible, sexual contact During birth ```

HPV symtoms (3)

Warts of oropharynx laryngeal papillomas (HPV-6 and -11) respiratory papillomatosis

respiratory papillomatosis (2)

hoarseness is usual symptom (signify obstructing HPV lesions) respiratory distress and secondary bacterial pneumonia in

Single oral papillomas are the most

benign epithelial tumors of the oral cavity

Anogenital warts

condylomata acuminata (90% caused by HPV-6 and -11)

Cervical papillomas | HPV is present in ---% of a cervical cancers

99.7

>---% of cervical carcinomas contain integrated HPV DNA

HPV (2) (and 31& 45) are high-risk types

16 and 18

pap smear

cells are scraped from the cervix and examined under a microscope to check for disease or other problems

HPV | vaccines (2)

Gardasil: HPV 16&18 (cervical cancer) Cervarix: HPV 16&18

``` The HPV (2) proteins are important for cancer development. They are the only 2 HPV proteins always expressed in ```

E6 and E7 | cervical cancer cells.

E7 protein of HPV prevents --- from controlling cell division

E7 protein of HPV prevents Rb from controlling cell division | 4

Similar to proteins of other viruses these proteins bind Rb complex and prevent Rb from negatively regulating E2f HPV E7 protein acts like the SV40 virus LT protein SV40 LT promotes disassembly of Rb-E2f complex. E2f is now free to activate transcription of cellular DNA synthesis genes