EBV, CMV, Viral Latency, and Cancer Flashcards
acute lytic infection
- viral infection that results in the production of progeny virus and lysis of the infected cell
acute lytic viral infections - initial infection event is followed by
- rapid, often exponential replication of the virus
acute symptoms of lytic viral infections due to
- tissue destruction due to virus replication
- side effects of host immune response
chronic lytic viral infection
- productive viral infection in a subset of cells
- continual infection/re-infection cycle
- ongoing shedding of virus from infected cells that does not immediately result in lysis.
types of chronic lytic infections
- chronic focal infection
- chronic diffuse infection
chronic focal infection
- a new subset of carrier cells produces virus
- infects neighboring cells
- initial cells replaced by new cells
- newly infected cells reinstate the process
chronic diffuse infection
- both infected cells and virus continue to replicate
- cells are not lysed by virus
- cells continue to shed virus for their life span
hepatitis C causes what kind of infection?
- chronic lytic infection
what type of replication does hepatitis C virus have
- persistent lytic replication
result of hepatitis C virus
- culminates in cirrhosis and/or hepatocellular carcinoma
the main difference between acute lytic and chronic infection is
- the time to clear the virus
acute infection time to clear the virus
- less than two weeks
chronic infection time to clear the virus
- weeks/months/years
what is latency in a virus?
- presence of viral nucleic acid in the absence of pre-formed infectious virus that has the ability to re-initiate lytic replication
the difference between chronic versus latent infection
- difference is in the molecular state of the virus
production of virus in latent infection
- latent infections do not produce infectious virus
product of virus in chronic infection
- chronic infections involve continual production of new viral particles
what is the viral genome maintained as in all latent viruses
- DNA
provirus
- viral genome integrated into host genome
episome
viral genome maintained as extra chromosomal DNA
EBV is in what virus family?
- herpesvirus 4
DNA in herpesvirus
- linear dsDNA
- in icosahedral core
virus particle in herpesvirus
- enveloped in lipid membrane
where does the lipid membrane come from in herpesvirus?
- lipid comes from the host cell
where is EBV’s site of latency
- lymphoid cells
where is CMV’s site of latency
- various cells
EBV transmitted by
- saliva
EBV initially infects
- epithelial cells in oropharynx
EBV spreads to
- blood
- infects B-cells via CD21 complement receptor
primary infection in EBV
- asymptomatic
when is EBV clinically apparent as infectious mono
- when primary infection occurs later in adolescents and young adults
clinical signs and symptoms of infectious mononucleosis
- fatigue
- fever
- sore throat
- lymphadenopathy
mononucleosis is the proliferation of
- mononuclear cells
- lymphocytes
infected B cells are recognized as
- atypical lymphocytes by cytotoxic T cells
immunologic test in EBV
- heterophiles antibodies
heterophile antibodies used
- define antibodies against poorly-defined or cross reacting antigens
how is EBV tested
- monospot test
- does not confirm infection
EBV specific antibodies
- IgM - early
- IgG - later
- VCA - viral capsid antigens
treatment of EBV
- acyclovir not effective
- no vaccine
EBV associated diseases
- life-threatening mono in children with X-linked lymphoproliferative syndrome
- hairy leukoplakia
- burkitt’s lymphoma
hairy leukoplakia symptoms
- whitish, nonmalignant lesions on the tongue
hairy leukoplakia found in which population
- immunocompromised patients, specially AIDS
Burkett’s lymphoma endemic in
- Africa
- New Guinea
Burkett’s lymphoma sporadic in
- US
- Western Europe
Burkett’s lymphoma associated with
- HIV
EBV latency
- establishes latency as episomall DNA in nucleus of infected B cells
- ONLY INFECTS B cells
latently infected cells produce
- IL-10 resulting in uncontrolled proliferation
two groups of genes mutated in cancer
- tumor suppressors
- proto-oncogenes
activity of tumor suppressors
- inhibit cell cycle progression
mutation in tumor suppressors
- loss of function
examples of tumor suppressors
- Rb
- p53
- p16
- ARF
- PTEN
porto-oncogenes activity
- stimulate cell cycle progression
mutation in cancer of proto-oncogenes
- gain of function
proto-oncogene is (wild type/mutant)
- wild type
oncogene is (wild type/mutant)
- mutant
examples of proto-oncogenes
- cyclin D1
- Mdm2
- myc
- ras
more divisions in EBV infected cells means
- more chances that unlikely mutations occur
CMV transmitted by
- transplacentally
- saliva
- genital secretions
- transfusions
- transplants
CMV on smear
- giant cell formation with intranuclear inclusions
- looks like owl eyes
most common cause of congenital abnormalities in the US
- CMV
CMV symptomatology for primary infections in kids and adults
- asymptomatic
CMV in 1st trimester of pregnancy
- cytomegalic inclusion disease causes defects in many organs
latently infected cells by CMV
- have unstable MHC1
- aren’t well recognized by CD8 T cells
CMV skin findings
- blueberry muffin lesions in neonates
heterophiles test in CMV
- heterophiles negative mono in immunocompetent individuals
symptoms of CMV in transplant patients
- pneumonia
- esophagitis
- hepatitis
infection of CMV in AIDS patients
- intestinal infections
- severe colitis
- diarrhea
- retinitis
CMV treatment
- ganciclovir and valgancyclovir
- no vaccine
why are heterophiles antibodies associated with infectious mono in EBV but not CMV
- EBV infects B cells which makes a lot of antibodies not specific for the virus
- CMV infects a host of cells
why does acyclovir not work well against EBV infection
- acyclovir must be activated by viral thymidine kinase
- only in infected cells
ganciclovir is activated by
- cellular kinase
