Viruses (Skildum) Flashcards
(146 cards)
1
Q
Colorado Tick Fever - family
A
reoviridae
2
Q
Colorado Tick Fever - genome
A
dsRNA, segmented
3
Q
Colorado Tick Fever - Envelope
A
no
4
Q
Colorado Tick Fever - Capsid
A
icosahedral
5
Q
Colorado Tick Fever - Baltimore
A
III (dsRNA)
6
Q
Colorado Tick Fever - Tropism
A
pro-erythroblasts (marrow) –> and then present in mature RBCs
7
Q
Colorado Tick Fever - pathologies
A
Colorado Tick Fever: Saddleback fever pattern (days of high fever, normal, and then maybe again), travel to mountain West
8
Q
Colorado Tick Fever - tx
A
supportive
9
Q
Colorado Tick Fever - vector
A
Dermacenter andersoni tick
10
Q
Colorado Tick Fever - geography and season
A
March – November
Mountainous western regions
11
Q
CTFV uses the __________________ strand of its genome for transcription and as a template for replication of the ________________ strand.
A
-RNA (transcribe to +strand = mRNA)
12
Q
Cytomegalovirus is same as
A
HHV5 (CMV)
13
Q
CMV - family
A
herpes (beta)
14
Q
CMV - genome
A
dsDNA
15
Q
CMV - envelope
A
yes
16
Q
CMV- capsid
A
icosahedral
17
Q
CMV - baltimore
A
I
18
Q
CMV - tropism
A
systemic (variety of cells); latent in CD34+ cells (monocyte –> macrophage)
19
Q
CMV - pathologies
A
CMV infectious mononucleosis: heterophile Ab negative, Owl’s eyes cells
Congenital systemic CMV: deafness
20
Q
CMV- tx
A
supportive; ganciclovir for immunocompromised patients
21
Q
HHV-6 HHV-7 - family
A
herpes
22
Q
HHV-6 HHV-7 - genome
A
dsDNA
23
Q
HHV-6 HHV-7 envelope
A
yes
24
Q
HHV-6 HHV-7 capsid
A
icosahedral
25
HHV-6 HHV-7 baltimore class
HHV-6 HHV-7
26
HHV-6 HHV-7 tropism
CD4+ T cells, others: PBMNCs, epithelial cells
27
HHV-6 HHV-7 pathologies
```
exanthem subitum (roseola) = rash taht develops after fever resolves,
heterophile Ab negative mononucleosis
```
28
EBV aka
HHV4
29
EBV family
herpes
30
EBV genome
dsDNA
31
EBV envelope
yes
32
EBV capsid
icosahedral
33
EBV baltimore
I
34
EBV tropism
acute: epithelial cells of oropharynx (supports lytic life cycle)
latent: B cells
35
EBV pathologies
EBV infectious mononucleosis: Heterophile Ab positive mono
Burkitt lymphoma: t(8:14)
Hodgkin & non-Hodgkin lymphoma
nasopharyngeal lymphoma
X-linked lymphoproliferative disease: inherited mutation in SAP adaptor
36
tx ebv
supoortive (mono)
37
Kaposi Sarcoma aka
HHV-8
38
Kaposi Sarcoma family
herpes
39
Kaposi Sarcoma genome
dsDNA
40
Kaposi Sarcoma envelope
yes
41
Kaposi Sarcoma capsid
icosahedral
42
Kaposi Sarcoma baltimore
I
43
Kaposi Sarcoma tropism
epithelial cells, b cells
44
Kaposi Sarcoma pathology
in immunocompromised patients only: Kaposi sarcoma, primary effusion lymphoma, multifocal castlemans disease
45
Kaposi sarcoma tx
Ganciclovir, cidofir, foscarnet
46
Parvovirus B19 family
parvovirus
47
Parvovirus B19 genome
ssDNA (+ or -)
48
Parvovirus B19 envelope
no
49
Parvovirus B19 capsid
icosahedral
50
Parvovirus B19 baltimore
II
51
Parvovirus B19 tropism
erythroid progenitor cells
52
Parvovirus B19 pathologies
erythema infectiosum: fiery red rash on cheek. Transient aplastic crisis: in patients with underlying anemia
53
tx Parvovirus B19
support
54
Human T Lymphocyte virus-1 family
Retrovirus
55
HTLV-1 genome
ssRNA +
56
HTLV-1 envelope
yes
57
HTLV-1 capsid
icosahedral
58
HTLV-1 baltimore
VI
59
HTLV tropism
T cells
HTLV-1 >CD4
HTLV-2>CD8
60
HTLV-1 pathologies
Acute T cell lymphoma / leukemia (ATL): Viral transcription factor Tax drives proliferation; blocks apoptosis.
HAM/TSP: Inflammation on the spine
61
HTLV treatment
chemotherapy/BMT
62
HIV family
retrovirus
63
HIV genome
ssRNA +
64
HIV envelope
yes
65
HIV capsid
icosahedral
66
HIV baltimore
VI
67
HIV tropism
CD4+ T cells (also CD4+ monocytes & macrophages, others)
68
HIV pathology
Acquired immunodeficiency syndrome: depletion of CD4 T cells allows opportunistic infections
69
HIV tx
Multiple anti-retroviral agents
70
Ebola family
filovirus
71
ebola genome
ssRNA -
72
ebola envelope
yes
73
ebola capsid
helical/complex
74
ebola baltimore class
V
75
ebola tropism
macrophages
76
ebola pathologies
hemorrhagic fever
77
ebola tx
supportive, working on it
78
what does Parvovirus B19 require to gain entry to host cell and establish infection
P blood antigen = B19V receptor, found on erythroid progenitor cells
79
How does parvovirus replicate
Enters nucleus, folds ssDNA back on itself in hairpin loop structure (self priming)
80
What is the relationship between viral protein NS1 and B19V pathogenesis?
NS1 affects cellular DNA and induces apoptosis of erythroid progenitor cells leading to a decrease in the production of erythrocytes (promotes NFkB binding site to IL-6 -- activation of polyclonal B cells to cause inflammation?)
81
How to dx parvovirus (beyond clinical signs)
serology for anti-pv IgG and IgM. IgM at time of rash, 3rd day of TAC. PCR could be used - but will be positive even in healthy individuals.
82
typical clinical presentation erythema infectiosum
Fever 7-10 days after exposure
| Then a Slapped cheek appearance and lacy exanthem rash for a few days, may spead
83
When does Transient aplastic crisis occur?
Parvovirus B19 in individuals already at risk for anemia --> disastrously low blood counts
84
Other conditions caused by B19V
Hydrops fetalis, meningitis, encephalitis, neuropathy
| ARthritis, arthralgia (NS-1 hyperinflammatory may lead to autoimmune antibodies)
85
how is CTFV infection diagnosed?
Virus isolated from whole blood by inoculation of cell cultures. RT-PCR can detect viral RNA in red blood cells and in plasma. Specific neutralizing antibodies appear in the 2nd wk of illness and can be detected by plaque reduction tests. Can also do ELISA or fluorescent antibody tests.
Usually clinical.
86
Malignancies associated with EBV
```
Nasopharyngeal carcinoma
Burkitt lymphoma
Hodgkin disease
Non-Hodgkin lymphoma
X-linked lymphoproliferative disease (extremely rare and severe--occurs with a certain an inborn error of metabolism)
```
87
How does EBV gain entry to B cells and establish infection
Viral envelope proteins gp350/220 bind the C3d complement receptor (aka CD21) --> endocytosis
Genome circularizes and immediate early, then early then late genes are expressed.
Viral particles then bud through cell membranes to make infectious particles.
88
EBV oncogene LMP1 function
The EBV oncogene LMP-1 functions as a constitutively active CD40. CD40 is normally responsible for CD4+ T-cell dependent activation of B cells.
89
What transcription factors does LMP-1 activate?
NF-kB
90
EBV oncogene LMP2 function
constitutively active B cell receptor, promoting MAPK activation and transcription of fos/jun (et a) regulated genes. Normally responsible for antigen dependent B cell activation.
91
What transcription factors are activated by LMP2?
fos/jun (et al) transcription factors
92
EBV oncogene EBNA3C function
The EBV oncogene EBNA3C functions to bind and activate cyclin D1 complexes, resulting in:
Hyperphosphorylation of retinoblastoma protein (Rb)
De-repression (i.e. activation) of E2F family transcription factors
Expression of genes that control DNA replication
Cell cycle progression
93
EBNA3C affects control what checkpoint
G1--> S
94
Classic triad of infectious mononucleosis
pharyngitis, lymphadenopathy, fever
95
What test is diagnostic for EBV IM
monospot
96
what does monospot detect
heterophile Abs produced by polyclonal expansion of B cells
97
presence of VCA-IgM in a blood indicates (EBV)
acute infection
98
presence of VCA-IgG in blood indicates (EBV)
previous infection
99
appearance of what in a blood smear is diagnostic for EBV
atypical lymphocytes
100
X linked lymphoproliferative disease presents as
Fuliminant infectious mononucleosis (FIM)
Median age for FIM is 3 years old; average survival after FIM is 1-2 months
Patients who survive FIM develop lymphoproliferative disorders and dysgammaglobulinemias
101
Molecular basis for X linked lymphoproliferative disease
mutation that results in non-functional SAP protein (SAP adapter protein that recruits kinases to immunological synapse)
SAP depletion results in deficiency of IL-4 production by T cells.
102
IL-4 normally signals
CD4 TH2 differentiation and regulates B cell class switching
103
How are HTLV-1 and HTLV-2 different?
HTLV-1: >CD4+; HTLV-2: >CD8+
| HTLV-1 causes Adult T-cell leukemia, and both 1 and 2 cause HTLV-associate myelopathy
104
What does Ebola virus bind and how to get into cell
attachment factors and receptors on the cell surface through the viral spike protein, glycoprotein (GP)
105
what happens after binding of ebola virus to outside of cell
The virus is then internalized into a macropinosome (step 2) and trafficked to an endosomal compartment containing the cysteine proteases cathepsin B (CatB) and CatL (step 3).
106
What do catB and catL do to ebola
These proteases digest GP to a 19 kDa form, which is then triggered to initiate fusion between the viral and endosomal membranes (step 4).
107
what happens after fusion of ebola membrane and endosomal membrane?
After fusion, the viral nucleocapsid is released into the cytoplasm, where the genome is replicated (step 5) and transcribed (step 6) with the aid of the viral proteins VP35, VP30 and L, and viral mRNAs are then translated (step 7).
108
GP protein production in ebola life cycle
mRNAs encoding GP are brought to the endoplasmic reticulum (ER) (step 8), where GP is synthesized, modified with N-linked sugars and trimerized. GP is further modified in the Golgi and delivered to the plasma membrane in secretory vesicles (step 9).
109
final assembly ebola life cycle
At the plasma membrane the ribonucleoprotein complex (RNA plus nucleoprotein (NP)) and associated viral proteins assemble with the membrane-associated proteins (matrix proteins VP24 and VP40, and GP), and the resultant virions bud from the cell surface (step 10). Non-structural forms of GP, including soluble GP (sGP), are also secreted (step 11).
110
pathogenesis ebola w/ tropism
First in DCs, monocytes and macrophages. Neutrophils see viral antigen and are activated (degranulate). As more virus, lymphocytes apoptose, see failure of immune response. (upregulate inhibitory molecules, PD1) infection spreads to many cells, ie hepatocytes. Too many cytokines.
111
Early signs of ebola infection
incubation: 2-21 days
Fever, fatigue, muscle pain, headache, sore throat
vomit, diarrhea, rash, kidney/liver issues, internal and external bleeding
112
Cause of death for patients who die of ebola
organ failure
113
How is HIV-2 different?
Less easily transmitted, period between infection and presentation is longer.
West africa, viral loads lower than HIV-1
114
Normal number CD4
Below what is Immunocompromised
Below what is AIDS
600-1200 normal
Below 500 IC
Below 200 AIDS
115
Role of CD4 T cells
combat viruses, bacteria, fungi, parasites, cancer
116
If CD4 positive T cells are depleted (HIV)
increased viral, fungal, and bacterial functions
| Increased risk for some malignancies (ie kaposi sarcoma)
117
What does HIV ELISA measure
Direct - antibody
| Indirect - antigen for p24 protein (encoded by gag)
118
Positive HIV-1 ELISA confirmed by
Wester blot - measures ab in pt serum with sample antigen separated by size
119
what tests are used to monitor health of people with hiv-1
CD4+ flow cytometry
| viral load
120
where is HTLV-2 more common
HTLV-2 endemic to American Indian tribes in North, Central and South America as well as Central African pygmies. Hyperendemic among injection drug users in NA and europe.
121
What molecular interaction allows HTLV to enter a cell?
HTLV binds host gp46 and fuses w/ host cell membrane → integrates into DNA → TAX-induced (affects CREB, CREm, NFkB, and NSF) viral gene transcription and REX induced translation or viral mRNA
122
How does HTLV become a provirus?
Once in cell, Reverse transcriptase (from virus) transcribes viral RNA into dsDNA. dsDNA (cDNA) is transported to nucleus (as a complex w/ p24 capsid protein and integrase and RT). Integrase helps insert DNA into host genome → lifelong infection.
LTRs (integration sites where provirus attaches to cellular DNA, regulatory)
123
What host genes are upregulated in HTLV-1 Tax?
21-bp enhancer, ***NF-kB binding site, serum-response element → cellular genes such as IL-2, IL-2R, fos, erb…
Overproduce IFN-gamma →inflammation
124
What host genes are downregulated by HTLV-1 Tax?
beta-polymerase gene = required for genomic stability (does base excision repair)
125
How does Tax contribute to T lymphocyte transformation in HTLV-1?
Upregulate proteins for cell growth → proliferation but downregulate pol B which leads to more genetic instability --> malignancy
126
clinical presentation ATL
Generalized lymphadenopathy, visceral involvement, hypercalcemia, cutaneous involvement (localized or diffuse, papules, nodules, plaques or patches or erythemoderma, w/ infiltration of malignant lymphocytes, pautrier’s microabscesses, lytic bone lesions, peripheral blood involvement (flower cells).
127
clinical presentation HTLV-1 Associated Myelopathy (HAM)
Chronic progressive demyelinating disease that affects spinal cord or white matter of the CNS.
May be associated with blood transfusion, or familial.
Mainly adults (females), some children younger than 10.
Subtle onset - Stiff gait, progressing to increasing spasticity and lower extremity weakness, back pain, urinary incontinence, impotence (men). Tingling, pins and needles, burning.
128
Malignancies associated with Kaposi Sarcoma virus
aposi
sarcoma, primary effusion lymphoma,
multifocal Castlemans disease
129
Kaposi Sarcoma virus vFLIP
homolog of a normal cellular protein that regulates apoptosis, FLIP. (FLIP inhibits formation of active caspase-8, always on so no apoptosis?_
130
KSV's vBcl-2
homolog of a normal cellular protein that regulates apoptosis, Bcl-2 (Bcl-2 inhibits apoptosis, so always on --> no apoptosis)
131
KSV's vGPCR
homolog of a normal cellular protein that regulates cell fate, GPCR (always growing).
132
KSV's vCyclin
homolog of normal cell protein that regulates apoptosis (Cyclin D1 = constitutively active --> always going through cell cycle)
133
Treatments for KSV target the
lytic phase - prevent reinfection only
134
Ganciclovir is the antiviral for
beta herpes virsues
135
Cidofir mechanism
viral DNA polymerase inhibitor
136
Cidofir effectiveness
Cidofovir is an antiviral drug that acts against many types of herpesvirus, and may be an effective treatment for Kaposi's sarcoma. Use it to treat CMV retinitis in AIDS PTs
137
Foscarnet mechanism
viral DNA polymerase inhibitor
138
How does HHV-7 differ from HHV-6?
```
HHV-6 can integrate into the
genome
HHV-6 infects peripheral blood mononuclear cells (PBMCs) and cells in the liver, salivary glands, endothelial cells, and central nervous system.
HHV-7 is more found in the saliva
than HHV-6
HHV-7 can be found in breast milk
while HHV-6 cannot
HHV-7 occurs later in life
```
139
exanthem subitum
roseola or sixth disease
| Fever then a rash
140
tx in uncomplicated exanthem subitum
Antipyretic, no antiviral
141
What can occur in adults infected with HHV6 and HHV7?
May be asymptomatic.
| If IC, may see mono, encephalitis, disseminated disease, pneumonitis, syncytial giant-cell hepatitis
142
typical presentation CMV infectious mononucleosis
Prolonged high fevers, sometimes w/ chills, fatigue, and malaise. Myalgia, headache, and splenomegaly are common but exudative pharyngitis and cervical lymphadenopathy are rare. Can develop rubelliform rash after exposure to ampicillin. Rare cases can get Guillain-Barré
Heterophile ab NEGATIVE.
143
What is measured in diagnosing CMV infection by enzyme linked immunoassays?
p65 in peripheral blood leukocytes
144
What type of cell in a blood smear indicates CMV infection
Owl's eye cells
145
Other conditions associated with CMV
Can cause congenital deafness, jaundice, thrombocytopenic purpura, hepatosplenomegaly, microcephaly, and mental retardation. For immunocompromised- hepatitis, penumonitis, esophagitis
146
Why isn't acyclovir effective for CMV infections?
Requires the first phosphorylation (no thymidine kinase)
