#14 Lymphotropic Herpes Flashcards
1
Q
Characteristics of Lymphotropic HSVs
- Replication and latency in cells including_____ origin
- Persistantant infection is balance btwn _______
A
lymhoid
lytic and latent
2
Q
γHSV—oncogenic:
A
EBV (HHV-4) and Kaposi’s Sarcoma Virks (HHV-8)
3
Q
EBV (HHV-4) and Kaposi’s Sarcoma Virks (HHV-8) are latent in
A
Latent in B cells and Plasma cells
4
Q
Human herpes- 6b
HHV-6b
Latent in
A
T lymphocyte
5
Q
CMV or Cytomegalovirus what type of herpesvirus
A
β Herpes virus:
6
Q
- Infected Cells
a. get very big, have inclusion bodies and characteristic OWLS eyes
A
CMV
7
Q
- Disease referred to as what for CMV
A
Cytomegalic inclusion body disease, CMV disease, Inclusion body disease
8
Q
HHV-5 (beta) is what herpes viurs
A
CMV, dsDNA, icosahedral
9
Q
Transmission of CMV
A
secretions-semen, cervix, blood, saliva, tears, breast milk, urine and feces, blood transfusion, organ transplant, and transplacental transmission
10
Q
CMV presentation in healthy adults
A
Asymptomatic in health adults: see mild mononucleosis or cold-like symptoms
11
Q
What is the leading cause of congential birth defects?
A
CMV (HHV5) beta HSV
a. mild to severe mental retardation, deaf, death b. TORCH: it’s the ‘C” and is an acroynm for viruses that cause congenital birt defects
12
Q
If you get CMV and are immunocompromised, what do we see?
A
- Symptomatic upon immunosuppresion
a. Chemo/organ transplant/HIV
13
Q
CMV persistant infection we see
A
atherosclerosis/ immunosenescenes/ neuroblastoma
14
Q
Stages of gene expression for CMV
how many genes does it express?
A
Stages of gene expression: immediate/early/ and late
—-. expresses over 750 proteins~ that’s a TON!
15
Q
CMV Encodes own _______ machinery
A
DNA repliation
thats why it so fucking huge
16
Q
CMV LYTIC Replication cycle
Binding/penetration happens withing ____ mins and we can see membrane fusion or endocytosis in the _______
A
30 mins
epithelial cell
17
Q
Once CMV Enters into cytoplasm
a. Sends tegument protein ______ to nucleus for transcrtiption
A
pp65
18
Q
What is the purpose of pp65 in CMV?
A
its a tegument protein CMV sends to nucleus for transcription
19
Q
- Transcription if CMV occurs in: ______
a. immediate early transcrtipion of DNA→ early transcription→ late transcription
A
nucleus
20
Q
For CMV:
DNA replication:
Encapsidation at :
Envelopment/release will take:
A
1-2 days
2-3 days
72-96 hours
21
Q
Lytic CMV infected Cell
1. infected cell the nucleus is HUGE because
A
a. virus in making TOS of viral DNA
22
Q
What ‘s special about the nucleus during the lytic cycle in CMV
A
See the nucleus bent arount the replicaiton cytosole
23
Q
Transmission of CMV
A
- Direct contact w/ virus containg secreations: semen/cervicle/blood/saliva/tears/breast milk/urine/poo
~ Inoculation onto mucosal site
24
Q
- Other routes not as common for CMV
A
blood transfussion, organ tranplants/ transplacental transmission
25
For CMV, shedding can occur:
| viral excreation starts at 1 month and shedding can contineu for months to >1 yrs
with or without symptoms
26
Highest rate of incidents and transmission for CMV
trasmission via daycares~~~ big population in children under 18 monts
27
CMV dissemination
CMV dissemination
1. Cell associated—poorly released from infected cell
2. Slow replication cycles
3. Lytic replication; occurs EVERYWHERE
4. Laten infectin: more in CD34+ hematopietic progenitor cells and monocytes
5. Frequency of reactivation: 1 in 10,000 of infected monocytes~ not a ton, but enough
28
Where does lytic replicaiton occur for CMV
everywhere
29
Location for latent infection of CMV
more in CD34+ hematopietic progenitor cells and monocytes
30
Innate immune response to CMV
Macrophage, INF and NK cells control but are insufficient to clear virus
31
2. Humoral response to CMV:
no role, but may limit re-infection.
| a. involves neutralizint antiBs directed agains surface antigens such as gB, gH, pp65, pUL-128
32
3. Cell mediated immune response to CMV:
keey CTLs will kill CMV infected cells
a. up to 10% of all CD8 T cells in body are directed against CMV (huge %!!!)
b. cytotoxic T cells are main players in fight CMV
33
main players to fight CMV
cytotoxit T cells
34
can host immune reponse completely take care of CMV
4. Immune response can’t completely control CMV
| Reinfection by different CMV variants occurs: high degree of intra-host genomic variability
35
Symptoms of CMV in healthy adults
mild disease and unappareant
a. see fever, fatigue, sore throat, headache for 2-3 weeks w/ slightly elevated ALT
slight increase in lymphotyces and swollen lymphnodes
36
Mononucleuosis
| a. Heterophile anitB is negative
CMV!!!!!
37
Key diagnostics for CMV
| serology
Serology: IgM not reliable--t IgG will indicate recent or distant past infection
IgG avidity increase w/ time and helps distinguish btwn recent and past infectin
38
See owls eye incluction body
CMV
| ds DNA linear, icosohedral herpesvirus with tegument
39
genome for CMV
ds DNA linear, icosohedral herpesvirus with tegument
40
TX of CMV
```
Ganciclovir (IV or valganciclovir)
Foscarnet (IV)
Cidofovir (IV)
CMV does NOT encode a thymidine kinase: acyclovir is less effective
Anit-CMV IgG products given in parallel
```
41
structual mimic of pyrophosphate will inhibit pyrophosphate binding site on viral DNA polym.
Foscarnet
42
synthetic 2’deoxycytidine analogue… doesn’t need phosphorylation and ≠viral DNA polymerase
Cidofovir
43
a. synthetic 2’deoxyguanosine analogue that’s activated by viral kinase
b. inhibits viral DNA polymerase
Ganciclovir
44
Congeinital CMV: common congenital infection
1. 1 in 150 babies infected with CMV at birth and 1 in 750 have birth defects (1st semester = worse outcome)
2. Only 14% women have heard of CMV: key to educate women in childbearing age to decrease exposure
CMV facts
45
3. Perinatal infectinon of CMV: at time of birth from
ervical secreations/transmission via milk an IG no clincal signs
46
Symptoms of congenital infection (CMV)
(poor outcome)
Petichial lesions/ small size/hepatoslenomegaly/jaundice
Permanent symptoms: hearing loss/ vision loss/mild-severe MR/Muskuloskeletal abnormatiles
47
(poor outcome)
Petichial lesions/ small size/hepatoslenomegaly/jaundice
Permanent symptoms: hearing loss/ vision loss/mild-severe MR/Muskuloskeletal abnormatiles
congenical CMV infection
48
CMV in immunosuppressed pts
Life threating: for transplant pts/ on immunosuppresants/undergoing chemo of HIV pts
Transplant pts: solid organ or hematopoietic stem cell
a. at risk for pneumonia/ fever/hepititis/ encephalitis/retinitis/ neuropathy
b. CMV donor and recepient status is evaluated
49
HIV with CMV
a.see retinits (rare if on HAART) or fever/esophatigis/ gastritis/colitis
50
βHHV:
human herpes virus 6b
51
Roseola virus:
Herpesverdia
HHV6b
ds DNA linear, icosohedral
52
Herpesverdia
HHV6b
ds DNA linear, icosohedral
roseolavirus
53
Roseolavirus:
viral genome can integrate into host chromosome: implications in transmission—INTEGRATES into host which is surprising bc this
a HUGE virus
54
Diseaes: in children for roseolaviurs (HHV6)
| 1.____ of children over 2 are seropositive
90%
55
Roseola HHV6b symptoms:
have high fever~ 4 days, irritable, maliase and lympadenopathy
Rash occurs in 10% of kids 12-24 hours after fever breaks
no sequele and common cause of admittance to ER for pts
56
have high fever~ 4 days, irritable, maliase and lympadenopathy
Rash occurs in 10% of kids 12-24 hours after fever breaks
no sequele and common cause of admittance to ER for pts
Roseola HHV6b
57
see a kid tht was really sick... kinda got better then had really bad rasah!
roseolavirus
58
Roseola can reactiate in SCT receptients and relpicates:
inside CD4+ T cells and site of latency
59
Where is the site of replication and latency for Roseolavirus
inside CD4+ cells
60
1st seen in Burkitt lymphoma in 64~~~ cancer causing virus
Seropositiveity: see over 95% are seropositive by 20yrs old
. 90% EBV +ve exhibit intermittent shedding w/out symptoms
Asymptomatic infections are common
EBV (HHV4) general
61
Genreal on EBV
HHV-4 (gamma)
ds DNA linear, icosohedral
yes to tegment and env
62
Transmission of EBV
saliva and blood
63
Infection path of EBV
Infect cells in blood stream (B-cells) and disseminate throughout body, Bind to epithelial cells intially and then go to B-cells which rapidly proliferate (primary mono) causing formation heterophile antibodies and activation of atypical downey T-Cells to control infection (cause mono symptoms), infection may also produce latency leading to reactivation and spread of virus or cancer
64
Disease caused by EBV
infectious mononucleossis
Post Transplant Lymphoproliferative Disorder (PTLD) and see low survivial
Lymphomas~~ B, T, and NK cell
65
Possible outcomes of infection of EBV:
replicate in B cells or epithelial cells
~~~latent infection in memory B cells and limits whre it infects the body
Stimulate and immortalize B cells
66
When first infected with EBV it will infect what cell tyep
B cells and then latently in memory B cells
67
EBV:
| slow replication, limited host range,bind epithelial cells of pharynx or ____and have early, and late gene expression,
B-cells
68
EBV encodies its own______machinery to replicate DNA and make new viral particles---
DNA replication
69
With EBV, reactivation of latently infected activated B-cells Latency _____- result of viral antigens in memory B cells cause cancers and
type I/II
70
Latency type_____-result of viral antigens in proliferating B cells cause infectious mono, and post-transplant lymphoproliferative disease
III
71
type causes mono and PTLD
type II
72
________ is the ONLY time you get mononucleossis (Lat III!!!)
Primary infection
73
see atypical T or ‘DOWNEY “ cells and Heterophile antiB (good diagnostics for mono d/t EBV)
EBV at Lat III
74
Humoral response to EBV
see neutralizing antiB which has no effect on virus SHED but good for antiB diagnostics
75
Cell mediated reponse to EBV
CD8 +T lymphs and NK cells—lysis of EBV infected cells
a. see loss of T cell fnx resulting in B cell proliferative diseaes
b. Mono results from rapid proliferation of atypical T cells—Downy cells
76
3. EBV diesae: overactive immune response: infectious mononucleosis and EBV mediated _______ imortalization and lack of effective immune control (PTLD)
B cell
77
lack of effective immune control in EBV can lead to
PTLD
78
During Cell mediated response to EBV: see loss of T cell fnx resulting in
B cell proliferative diseaes
79
EBV-mediated B cell proliferative disease
a. immunosuppresive therapy activates infection and seen in 1-33% of organ transplants
b. w/in first year after transplant and arises in donor B cells or reactivation in recepient
c. low risk if graft contains donor T cells—if there are already T cells that work against EBV
Post Transplant Lymphoproliferatieve disorder
80
EBV mononucleosis test
a. test for heterophile antiB by agglutination of animal RBCs!!! Key.. animal blood will agglutinate from the heterophile antiBs
81
Lab test for PTLD
flourescent int situ hybridization to EBER RNA in neoplastic cells and NAT PCR
82
Burkitts lymphoma
a. B cell lymphoma of jaw and face seen in kids in africa
b. associated wth chromosomal translocation btwn chr 8 and 14
c. IgG promoter-myc prot-oncogene
General on Burkits
83
1. Burkitts lymphoma
B cell lymphoma of jaw and face seen in kids in africa associated wth chromosomal translocation btwn chr
IgG promoter-myc prot-oncogene
8 and 14
84
EBV DNA in epithelial tumor cells and seen in china/alaska/E. Africa
Nasopharyngeal epithelial carcinoma:
85
Disease: assocaited with KS, primary effusion lymhoma (PEL) and muticentric casteman disease (MCD)
Kaposis sarcoma
| HHV8 (gamma)
86
Kaposis Sarcoma: general
HHV-8
gamma Herpes virus
dsDNA
87
Kaposis Replication in what cells:
CD19+ periperal B cells, endothelial cells, monocytes and epithelial cells
