Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CMBM Exam 4 > Herpes > Flashcards

Herpes Flashcards

1
Q

Herpes Latency Key Points

A
  • Latency produces a chronic infection

*latently infected cells are not recognized as being infected by CD8+ T cells, thus they are not cleared

*virus is not actively replicating, thus there is no available target for antivirals to act upon

*herpes genome maintained as circular, extra-chromosomal DNA

  • Limited transcription generates LATs (latency-assoc. transcripts)

*LATs do not encode a viral protein

*encode a regulatory microRNA (miRNA)

*miRNAs inhibit expression of viral genes

  • Some heresviruses express a few viral proteins to help maintain latency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Herpes Reactivation Key Points

A
  • Reactivation

*may or may not result in clincal disease, however, infected individual is infectious and can transmit virus

*infection is endogenous and does not require re-exposure to the virus

*may be frequent in immunocompromised hosts

*recurrent infections are less severe, more localized and cleared more quickly b/c of immunological memory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Herpes Productive Infection Key points

A
  • Viral gene expression and replication of the genome occurs in stages:

*immediate-early (alpha) genes

*early (beta) genes (genome replication)

*late (gamma) genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Cell types infected by herpesviruses in vivo graph

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Herpes clinical manifestation of infection chart

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Herpes virus attachment

A
  • Alpha: HSV-1, HSV-2, VZV

*Initial attachment via heparin sulfate (glycosaminoglycan found on most cells)

*Tighter attachment via a variety of cell surface receptors, collectively called herpesvirus entry mediators (HVEM)

  • EBV (gamma virus)

*receptor for C3d component of complement (called CD211 or CR2); receptor present on B-cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Herpes virus entry and uncoating

A
  • Viral/cell fusion at the plasma membrane or receptore mediated endocytosis
  • Capsid and some tegument proteins migrate to the nucleus, other proteins remain in the cytoplasm

*CMV tegument contains mRNA to help initiate viral replication

  • Uncoating occurs at the nuclear membrane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

EBV Latency

A
  • Occurs in B-cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Acyclovir

A
  • Nucleoside (guanosine) analogue that inhibits productive herpesvirus replication
  • Antiviral drug that is only active in an infected cell during productive infection
  • MOA:

*requires phosphorylation to be acitve

*1st phosphate added by a virus specific enzyme, thymidine kinase (more actively phosphorylated by HSV’s than VZV’s)

*2nd and 3rd phosphates added by cellular enzymes

*competitively inhibits dGTP for insertion into DNA

*lacks a 3’-OH group so it can not accept a base; chain termination

Acyclovir-resistant HSV w/thymidine kinase mutations will still be susceptible to cidofovir

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Ganciclovir

A
  • Guanosine analogue
  • Active against CMV
  • MOA:

*phosphorylated by a protein kinase phosphotransferase (UL97) encoded by CMV

*competitively inhibits incorporation of dGTP into DNA; chain termination

*cellular enzymes can also phosphorylate ganciclovir; some toxicity

*inhibits viral DNA polymerase preferentially over cellular DNA polymerase

*has activity against other herpesviruses; HSV, VZV, EBV, HHV-6 and HHV-8

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Cidofovir

A
  • Cytidine analogue
  • Already has 1 phosphate group on it so its going to be active in both an infected and non-infected cell
  • MOA:

*Has 1 phosphate; 2nd and 3rd are added by cellular enzymes

*Higher affinity for viral DNA polymerases than cellular DNA polymerases

*Competes w/dCTP for incorporation into DNA

Acyclovir-resistant HSV w/thymidine kinase mutations will still be susceptible to cidofovir

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Foscarnet

A
  • Pyrophosphate analogue
  • Prevents cleavage of pyrophosphate from dNTPs, stopping DNA synthesis
  • Binds to herpesvirus DNA polymerases and HIV reverse transcriptase
  • Ganciclovir and cidofovir- resistant isolates of CMV are usually still susceptible to foscarnet
  • Higher affinity for viral polymerases than cellular polymerases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

HSV types of infection

A
  • Encephalitis usally HSV-1
  • Meningitis usually HSV-2
  • Encephalitis assoc. w/neonatal herpes usally HSV-2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

HSV-1 Primary Infection

A
  • Localized throughout the mouth
  • Enters neurons at site of infection and travels via retrograde transport to the trigeminal ganglion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

HSV-2 Primary Infection

A
  • Remains localized at the genital mucosa
  • Enters neurons at site of infection
  • Travels via retrograde transport to the sacral ganglion where it establishes latent infection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

VZV Primary Infection

A
17
Q

HSV vs VZV Reactivation chart

A
18
Q

Exanthem subitum

A
  • AKA roseola, sixth disease) in infants
  • Assoc. with infection of herpesviruses 6 or 7
  • May cause febrile seizure w/o rash in infants (6 or 7)
  • May contribute to morbidity in AIDS and following transplants
19
Q

Epstein-Barr Virus

A
  • Cell tropism determined by presence of EBV receptor (CR2/CD21)
  • Expressed on B cells and epithelial cells of the oropharynx and nasopharynx

*B cells- productive, immortalizing or latent infection; transformation

*Epithelial cells- productive infection; transformation

  • MHC class II molecules are used as co-receptors
20
Q

EBV Latent Infection

A
  • Occurs in infected B cells that differentiate into memory cells in the presence of complement T cells

*T cells eliminate EBV-activated (immortalized) B cells

  • Genome remains non-integrated and replicates during cell division

*no protein synthesis occurs during latency except for Epstein-Barr nuclear antigen 1 (EBNA-1); expressed during cell division to retain the viral genome in cells

21
Q

EBV Immortalization of B cells

A
  • B cells are stimulated to divide and secrete antibody

*EBNA 2 essential for immortalization

*Polyclonal activation

*Heterophile antibodies

  • EBV-activate B cells are eliminated by T cells

*activation and proliferation of T cells => mononucleosis

22
Q

Infectious Mononucleosis

A
  • T cell response to EBV-infected/immortalized B cells
  • Symptoms:

*lymphadenopathy, splenomegaly and exudative pharyngitis

*fatigue, fever, hepatosplenomegaly

*rash in patients treated w/ amoxicillin for suspected strep throat

  • Dx

*Increase WBCs; large, atypical T cells (Downey cells)

*Detect heterophile antibodies

+Monospot test, EIA

+Detected from end of 1wk for several months

*Serology

23
Q

EBV Serological data chart

A
24
Q

EBV Reactivation

A
  • Virus latently infects memory B cells
  • Activation of latently infected memory B cells allows for transcription of ZEBRA

*ZEBRA turns on expression of immediate early genes, initiating productive infection

  • Common in tonsils and oropharynx

*virus is shed in the saliva

  • Reactivation is asymptomatic but individual is infectious
25
Q

Serology for EBV

A
  • Acute infection is confirmed by detection of:

*IgM to VCA

*VCA antibody, but no EBNA antibody (early acute)

*EA antibody (detected after VCA antibody)

  • alpha-EBNA antibody requires lysis of infected cells

*occurs as T cells clear the infection

*assoc. w/convalescence/resolution of infection

  • Detection of both VCA IgG and EBNA antibodies indicates previous infection
26
Q

EBV Serology Chart

A

CMBM Exam 4 (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions