Retrovirus-AuCoin Flashcards
(125 cards)
1
Q
What kind of virus is HTLV (human T-lymphotropic virus)?
A
an oncovirus and a retroviridae
2
Q
How do you get spread of HTLV?
A
via spread by infected lymphocytes (CD4+ T cells)
3
Q
Where is the HTLV virus present in the fluids?
A
semen, blood and breast milk
4
Q
How long is the incubation period for adult T-cell leukemia (ATL)?
A
20-50 years
5
Q
What is the clinical presentation of HTLV and ATL?
A
increased skin lesions, leukemia cells, hepatosplenomegaly and hypercalcemia (increased PTHRP)
6
Q
How do you diagnose HTVL?
A
ELISA for antibody (serology)
7
Q
Is there a vaccine or specific therapy for HTLV?
A
No vaccine or specific therapy
8
Q
How does HIV work?
A
gp120 on HIV binds CD4 receptor on T cells, monocytes, and dendritic cells.
9
Q
How is HIV transmitted?
A
by sexual contact, blood, IV drug use and vertically
10
Q
What are common in HIV?
A
opportunistsic microbial infections
11
Q
What is the acute phase of HIV?
A
“flu-like symptoms” followed by clinical latency period of weight loss, night sweats, fatigue, and lymphadenopathy
12
Q
How long does it take for HIV to progress to AID?
A
10 years
13
Q
What is the definition of AIDS?
A
CD4+ T cell count of 200 cells/ul (normal 800-1200 cells/ ul)
14
Q
How do you diagnose HIV?
A
serology and RT PCR to quantitate viral load
15
Q
What is the therapy for HIV/AIDS?
A
HAART (high active anti-retroviral therapy)
16
Q
Is there a vaccine for HIV/AIDS?
A
no vaccine
17
Q
What is the structure of retroviruses?
A
enveloped, (+) strand RNA viruses
18
Q
What do retroviruses encode?
A
an RNA-dependent DNA polymerase (reverse transcriptase [RT]
19
Q
How does the retrovirus replicate?
A
- Retroviruses encode an RNA-dependent DNA polymerase
- Replicates through a DNA intermediate
- DNA copy of the viral genome is then integrated into the host chromosome to become a cellular gene- provirus
20
Q
What was the first retrovirus to be isolated it produced solid tumors in chickens?
A
Rous sarcoma virus
21
Q
Other cancer causing retroviruses are classified as (blank) or (blank)
A
RNA tumor viruses or oncornaviruses
22
Q
How do RNA tumor viruses or oncornaviruses work?
A
these viruses alter cellular growth by expressing analogues of cellular growth controlling genes (oncogenes) (v-src)
23
Q
What was the first retrovirus found to be associated with human disease? Where did they get it from?
A
HTLV-1
T-cell leukemia
24
Q
How are retroviruses classified?
A
by disease they cause
by tissue tropism and host range
by virion morphology
by genetic complexity
25
The (blank) include only the retroviruses that can immortalize or transform target tissue
oncoviruses (HTLV)
26
The (blank) are associated with neurologic and immunosuppresive diseases.
lentiviruses (HIV)
27
What are the three subfamilies of retroviruses?
oncovirinae (HTLV1,2,5)
Lentivirinae (HTLV 1, 2)
Spumavirinae
28
What is the first isolated human retrovirus, however not associated with a disease?
spumavirinae
29
What is the struture of retroviruses?
spherical, enveloped, RNA viruses of 80-120nm
Envelope contains viral glycoproteins and is acquired by the plasma membrane
The envelope surrounds a capsid that contains two identical copies of the (+) strand RNA genome
30
How big is the RNA genome?
9 kilobases
31
The virion also contains what enzymes?
10-50 copies of the reverse transcriptase and integrase enzymes and two cellular transfer RNA (tRNAs)
32
The tRNAs found inside a virion are base-paired to each copy of the genome to be used as a (blank) for the reverse transcriptase.
primer
33
All retroviruses include three major genes that encode polyproteins. What are they?
Gag-> group specific antigen
Pol-> polymerase (reverse transcriptase, protease, integrase)
Env-> envelope (glycoproteins- gp120 and gp41 for HIV)
34
What are found at each end of the retrovirus genome?
long terminal repeat sequences (LTR) that contain promoters and enhancers to bind cellular transcription factors.
35
Complex retroviruses, HTLV and HIV encode several (blank) that require more complex transcriptional processing (splicing).
virulence-enhancing proteins
36
The viral glycoproteins are produced by (blank) of the polyprotein encoded by env gene
proteolytic cleavage
37
Gp160 of HIV is cleaved into (blank) and (blank)
gp41 and gp120
38
What do gp41 and gp120 form?
the trimer spikes (lollipop) that are visible on the virion surface
39
What does gp120 bind to? What does this do?
cell surface receptors
| determines the tissue tropism of the virus, it is recognized by neutralizing antibodies
40
gp120 is extensively (blank) and its antigenicity and receptors speficity can (blank) during the course of a chronic HIV infection. These factors impede immune clearance of the virus
glycosylated
| drift
41
(bank) promotes cell fusion
gp41
42
How does HIV replicate?
replication begins with gp120 (trimer) binding to the T cell CD4 receptor and a second G protein coupled chemokine receptor (co-receptor) called CCR5 (expresse on macrophages, and other T cells)
43
During chronic HIV infection, what happens to the env gene?
it mutates and gp120 can bind to CXCR4 (chemokine receptor which is expressed primarily on T cells)
44
What happens when HIV binds the co-receptor CCR5?
brings the viral envelope and the cell plasma membrane close and allows the gp41 to promote membrane fusion
45
In HIV replication what does the (+) sense genome do?
it is released into the cytoplasm and RT (using the tRNA as a primer) synthesizes a complementary (-) strand DNA (cDNA)
46
In HIV replication, what else does RT act as?
as a ribonuclease H and degrades the (+) RNA of the hybrid and then synthesizes the (+) strand of DNA to form the cDNA
47
RT is very (blank) prone. What is the mutation rate? WHat does this allow for?
error
1 error per 2000 bases
the evolution of new strains which may alter pathogenicity and promote immune evasion/selection
48
What happens to the viral cDNA created by HIV?
it is delivered to the nucleus and is integrated into host chromosome by the integrase enzyme
49
What do you called viral integrate DNA?
provirus
50
How do you get viral genome to integrate into the the host DNA?
with long terminal repeats (LTR)
51
What do LTRs contain?
enhancer and promoter sequences for regulation of trancription
52
(Blank) transcribes the host provirus into full length RNA whch is processed into gag, gag-pol or env. What happens to these full length transcripts?
Host RNA pol II
| They can be assembles into new virions
53
The provirus acts as a cellular (blank)
gene
54
THe provirus acts as a cellular gene, replication depends on host cell recognition of (Blank and blank) encoded in the LTR region
enhancers and promoters
55
HIV replication is also regulated by many (blank) genes
accessory
56
What accessory gene product is this:
| regulation of RNA splicing and promotion of export to the cytoplasm
rev
57
What acessory gene product is this:
| transactivation of viral and cellular genes
tat
58
What accesory gene product is this:
| decreases cell surface CD4; T cell activation; progression to AIDS
nef
59
What accesory gene product is this:
| transport of complementary DNA to nucleus arresting of cell growth
vpr
60
What accesory gene product is this:
| virus infectivity, promotion of assembly, blocks a celluar antiviral protein
vif
61
What accesory gene product is this:
| faciliates virion assemble and release
vpu
62
The proteins translated from gag, gag-pol, and env mRNAs are synthesized as (blank) and then are (blank) to functional proteins.
polyproteins
| cleaved
63
The proteins translated for (blank), (blank) and (blank) mRNAs are synthesized as polyproteins and the cleaved to functional proteins.
gag, gag-pol, env
64
THe viral glycoproteins are translated on (blank) followed by glycosylation in (Blank) and delivery to the (blank) to undergo (blank)
RER
ER
Golgi
secretory pathway
65
The gag and gag-pol polyproteins bind to the (Blank)
plasma membrane containing the envelope glycoprotein
66
Two copies of the HIV genome and the cellular (blank) molecules promote budding of virion
tRNA
67
After envelopment and release from the cell, what happens?
the viral protease cleaves the gag and gag-pol polyproteins to release the reverse transcriptase and form the virion core
68
The major determinant in the pathogenesis and disease caused by HIV is the virus (Blank) for (Blank and blank) cells
tropism
CD4-expressing T cells and myeloid cells
(monocytes, macrophages, dendritic cells, and microglial cells of the brain)
69
HIV virus causes persistent low-level productive and latent infection of (Blank and blank) cells
myeloid and memory T cels
70
Viruses causes (blank) formation, with cells expressing large amounts of (blank) antigen; subsequent (blank) occurs
syncytia
CD4
lysis
71
HIV virus reduces (blank) cell numbers and (blank) and helper-cell maintenance of what cells?
CD4 T cells
CD8 T cell, macrophage, and other cell functions
(CD8 T cell numbers and macrophage function decrease)
72
So what is a quick an dirty over view of HIV pathogenesis?
HIV enters body-> infects macrophages-> messes with them, and infects CD4 , messes with them.
Results in immune dysregulation, systemic opportunistic infections, Kaposis sarcoma, lymphoma)
73
During sexual transmission, HIV infects (blank)
mucosal surfaces
74
Those who are deficient in (blank) are resistant to HIV infection.
CCR5
75
Persistent HIV infection in macrophages, DCs, memory T cells, and hematopoietic stem cells serves as (Blank)
major reservoirs and means of transmission
76
Development of the symptoms of AIDS corelates with (blank) release of virus into the blood and a decrease in (blank)
increased
| CD4 T cells
77
THe (blank) protein promotes the progression of HIV infection to AIDS (nonprogressors).
nef
78
During the actue phase of the infection, there is a large (blank)
burst of virus production
79
T cell proliferation and responses to the infected cells promotes a (blank) syndrom
mononucleosis-like syndrome
80
Virus levels in the blood decrease during a clinically (blank), but viral resplication continues in the (blank)
latent period
| lymph nodes
81
Late in the disease (HIV), virus levels in blood decrease, (blank) levels signif decrease. (blank) levels also decrease. THe structure of the (Blank) is destroyed, and the patient becomes immunosuppressed.
CD4 levels
CD8 levels
lymph node
82
When do you get acute HIV syndrome, wide issemination of virus, seeding of lymphoid organs?
6 weeks
83
After the first drop after the primary infection, when do CD4 cells begin to increase slightly again? Then what happens?
at 6 weeks
| at 12 weeks they decline rapidly
84
When do you see constitutional systems?
opportunistic diseases?
death?
8 weeks
10 weeks
11 weeks
85
Why is AIDS so bad?
because your CD4 cels are unable to be activated to release cytokines required for activation of macrophages, other T cells, B cells and NK cells
86
What kind of immune responses are incapacitated in AIDS?
antigen-specific (especially cellular immune responses)
87
Since your antigen-specific immune response is incapacitated in aids, what will this cause?
an outgrowth of many opportunistic intracellular infections
88
HIV can aso cause neurologic abnormalities. What cells are mostly affected in this cause? WHat do they do?
microglial cells
macrophages
release neurotoxic substances or chemotactic factors that promote inflammatory responses and neural death in the brain
89
What do TCR bind?
short linear proteloytically cleave viral peptides
90
What kind of opportunistic infection is this:
toxoplamosis of the brain
cryptosporidiosis with diarrhea
isoproiasis with diarrhea
protozoal
91
What kind of opportunistic infection is this:
Candidiasis of the esophagus, trachea, and lungs
pneumocystis jirovecci (previously called pneumocystis carinii) pneumonia
cryptococcosis
histoplasmosis
coccidioidmycosis
Fungal
92
What kind of opportunistic infection is this:
cytomegalovirus disease
HSV infection (persistent or disseminated)
Progressive multifocal leukoencephalopathy (JC virus)
Hairy luekoplakia (EBV)
Viral
93
What kind of opportunistic infection is this:
mycobacterium avium intracellulare complex (disseminated)
Any 'atypical' mycobacterial disease
extrapulmonary TB
Salmonella septicemia (recurrent)
pyogenic bacterial infections (multiple or recurrent)
Bacterial
94
What kind of opportunistic infection is this:
karposi sarcoma
primary lymphoma of the brain
other non-hodgkin lymphomas
opportuistic neoplasms
95
The onset of AIDS correlates with a reduction in the number of (Blank) cells to less than 350 cells/ul and increased levels of virus
CD4 T cells
96
Full blown AIDS occurs when the CD4 T-cell counts are less than (blank)
200 cells/ul
97
Full blown aids has a viral load greater than (blank) and involves the onset of more significant disease
75,000 copies/ml
98
(blank) which is weight loss an dirrhead for more than 1 month and opportunistic infections and dementia are al part of HIV
HIV wasting syndrome
99
T or F
| Lymphadenopathy develops in AIDs
T
100
(blank) may result from opportunistic infection or HIV infection of the macrophages and microglial cells of the brain
AIDS-related dementia
101
What are the clinical manifestations of AIDS-related dementia?
slow deterioration of their intellectual abilities and exhibit other signs of a neurological disorder
(similiar to the signs of early stages of Alzheimer disease)
102
In the US, neurological complications are seen in more than (blank) percent of adults with AIDS
50
103
T or F
| frequency of dementia has decreased with HAART
T
104
What are the disease viral factors of HIV?
enveloped virus is easily inactivated and must be transmitted in body fluids
disease has a long prodromal period
virus can be shed before development of identifiable symptoms
105
How is HIV transmitted
virus is present in blood, semen, and vaginal secretions
IV drug abusers, sexually active people with many partners, prostitutes, newborns of HIV pos mothers
Blood and organ transplant recipients and hemophiliacs treated before 1985
106
What do antiviral drugs do?
limit progression of disease
107
The chronic nature of HIV alows the use of (blank) tests
serologic
108
Can serological test identify recently infected people?
no
109
How can you identify recent infection or late-stage disease?
by large quantities of viral RNA in blood, the p24 viral antigen, or the detection of RT enzyme
110
The ration of CD4/CD8 lymphocytes are (blank) in HIV patients
low
111
Anti-HIV therapy is currently given as a cocktail of several antiviral drugs termed (blank)
highy active antiretroviral treatment (HAART)
112
Why does HIV treatment use a cockatil of drugs?
because using a mixture of drugs with different MOAs has less potential to select for resistance
113
Multidrug therapy can reduce blood levels of virus to nearly (Blank) and reduce morbidity and mortality in many patients with advanced AIDS.
zero
114
When should you give HAART?
CD4 count less than 350 cells/ul (stronly recommended); CD4 count 350-500 cells/ul (appears to be beneficial)
OR
if viral loads are high (greater than 100,000 l) even if CD4 normals are greater than 350/ul
115
(blank) is also suggested for post-exposure prophylaxis if HIV is detected in the individual
Therapy
116
Whats going on with vaccine development?
protein subunit vaccines with gp120 or its precursor gp 160 elicit only antibody to a single strain of HIV and have not been successful
117
The most recent HIV vaccines prime T cell responses with ....?
vaccinia
canarypox
herpesvirus
defective adenovirus vector
118
A vaccien generating antibody against the (blank) of gp120 is under investigation and may elicit neutralizing antibody to most HIV strains
CD4 binding site
119
What are the four major groups of AIDS treament?
nuceloside analog
reverse transcriptase inhibitor
protease inhibitor
fusion inhibitor
120
How do nucleoside analogs work?
by inhibiting viral polymerse by incorporating a terminal nucleoside
121
How do reverse transcriptase inhibitor work?
binds to reverse trancriptase
122
How does protease inhibitor work?
inhibits the viral protease that is required at the late stage of the HIV replicative cycle
123
How do fusion inhibitors work?
blocks viral and cellular membrane fusion step involved in entry of HIV into cells
124
Whats this poor guy got?
AIDS :( (HIV)
125
A 60-year-old immigrant for the Caribbean Islands was seen by a physician with complaints of persistent skin rash, fatigue, swollen glands in the groin and under arms and a distended abdomen. Physical exam revealed an enlarged liver and spleen and extensive skin rashes. Laboratory finding demonstrated a marked lymphocytosis with pleiotropic features, elevated LDH and hypercalcemia
HTLV
