RetroViruses, AIDS, & Tumor VIruses Flashcards
(106 cards)
1
Q
who discovered Retroviruses
A
1911 by Peton Rous
2
Q
first retrovirus
A
Rous Sarcoma Virus
3
Q
who discovered reverse transcriptase
A
David Baltimore and Howard Temin in 1970
4
Q
Involvement in finding reverse transcriptase
A
Temin had the theory; baltimore/temin found the enzyme
5
Q
Isolation of the first retrovirus for human disease
A
1981 by Bob Gallo and associates who isolated HTLV-1
6
Q
The 4H club risk group for Retroviruses
A
Homosexual men
Heroin addicts
Haitians
hemophiliacs
7
Q
what did the 4H club die of
A
of normally benign opportunistics infections in the U.S.- AIDS (acquired immune deficiency syndrome
8
Q
Disocovery of HIV-1
A
1980: MOntagnier and assocaites in paris and Gallo and colleagues at NIH isoluate HIV_1 from patients with lymphadenopathy and AIDS
9
Q
where was HIV-2 discovered
A
In west africa in 1986
10
Q
similarity of HIV-1 and HIV-2
A
HIV-2 RNA sequence is similar to HIV-1 (40%). HIV-2 is mostly heterosexual.
11
Q
Origin of HIV
A
Evolved from simian virus in Africa (SIV) and spread through the rest of the world due to an increasingly mobile pop and aberrant sex
SIV>HIV-2>HIV-1 and human infection in 1930
12
Q
how mnay retroviruses are there
A
large and diverse group of viruses
13
Q
replication cycle similarity of retroviruses
A
Unique, with a DNA intermediate despite using RNA
14
Q
Retroviruses in vertebrates
A
ubiquitous
15
Q
do most retroviruses cause damage
A
no, most are benign
but other have significant pathogenicity and cause diseas and cancer
16
Q
2 subfamilies of Retroviruses
A
Orthoretroviridae
Spumaviridae
17
Q
Genome of Retroviruses
A
(+)ssRNA
diploid, identical copies
18
Q
Virion of Retrovirues
A
Enveloped
19
Q
proteins of Retroviruses
A
Reverse transcriptase (RNA-> DNA, DNA-> DNA
Integrase
Protease
20
Q
How are Retroviruses characterized historically
A
nucleocapsid strucutre and location in the particle
21
Q
how are retroviruses classified now
A
genome contents used to classify as simple or complex
22
Q
Simple retroviruses encode what genes
A
Gag
Pro
Pol
Env
23
Q
Complex retroviruses encode
A
all what simple retroviruses encode plus more
24
Q
replication cycle of a Retrovirus
A
Attachment Entry Reverse transcription Integration Transcription from provirus Translation Assembly release Maturation - protease activity
25
what occures in retrovirus reverse transcription
ssRNA genome to dsDNA
26
what occures in retrovirus integration
Virus dsDNA into host making a provirus
27
how does a retrovirus enter the cell
due to membrane fusion at the cellular membrane due to receptor mediated endocytosis
28
The defining feature of retroviruses
Reverese transcription
29
when does reverse transcription begin
initiates once nucleocapside is in cytoplasm (neeed higher level of NTPs)
30
what prevents reverse transcription
Low NTP levels
31
where does Reverse transcription occur
within a large complex similar to nucleocapside
32
what happens if reverse transcription does not occur for a retrovirus
infection cannot progress
33
why is Reverse Transcriptase promiscuous
can fall off one genome copy and then continue on another
34
Why would promiscuous Reverese transcription be silent
When copies are identical
35
what happens when different genomes are in the virion of a retrovirus
many different recombinations
36
why are Retrocviruses difficult to vacinate
since Reverse transcriptase can move from one genome to anther, it changes antigens of the retrovirus
37
what must a retrovirus have access to, in order to inegrate
must access the nucleus
38
when does a retrovirus access the nucleus during integration
access during mitosis - requires dividng cell
| also can do importation to infect non-deviding cells
39
how does a retrovius integrate
3 prime end of dsDNA from the virus genome is processed/opened up
Attacks target DNA creating a Nick in it
Host then repares DNA and acidentally adds the Virus genome
40
How can virus DNA be removed
INtegration of Virus DNA is permanent and cannot be removed
41
what happens if Virus DNA is integrated into the germ-line
provius becomes inherited and is called endogenous
42
what negative effect can integration of retrovirus cause
may disrupt host genes causing diseases such as cancer
43
Oncogenes for integration
Transcription factors
Secreted growth factors
GRowth factor receptors
Cell signal transduction pathways
44
effecienct of retrovirus replication
many defective viruses are made during replication (v. sloppy)
missing at least one of gag, pol, or env
45
what is required for retrovirus infection to make progeny
Require complementary infection
46
what can happen when Retroviruses carry oncogenes
oncogenes
47
do all retroviruses cause problems?
NO, can be benign
48
are most retroviruses cytopathic
no
49
effect of benign retroviruses on the cell
little impact to cell replication and physiology
| Chronic infection exert small demand on cell and host resources
50
How does the host respond to a benign retrovirus
can cause Viremia and elicit an immune response, bt host animals may live normal lives for months and years
never eliminated by the host
51
Types of Retroviruses that cause disease
Slow Retroviruses
Cytopathic retroviruses
Acute transforming viruses
52
what is the effect of a slow retrovirus
Like High-level mutagenesis
53
Eventual result of a slow retrovirus
Results in humorigenesis
54
how many Retroviruses carry cytopathic genes
Minority
55
What do Cytopathic retroviruses do
Cause tissue damage directly
56
what do Acute transforming viruses do
Induce rapid tumor formation
57
How do Acute transforming viruses lead to rapid tumor formation
carry host genes (mitogenic or antiapoptiotic
| Replication defective because host gene replaces an essential gene
58
Types of Human T-Cell Leukemia Virus (HTLV)
4:1,2,3,4
59
what type of HTLV is most often associated with humans
HLTV-1
60
what type of virus is HTLV
Deltaretrovirus
61
how does HTLV first isolated
in patients with cutaneous T-cell lymphoma in the 1970s
62
what forms when the Retrovirus first assembles
an immature virus
63
what happens to turn an immature virus into a mature one
proteases allow the immature to become mature and now it can replicate and infect
64
how many people are infected with HRLV-1
Millions of people world wide
65
How is HTLV-1 transmitted person to person
mother to child via breastfeding (endemic areas)
Sharing needles for drugs users
Blood transfusions
Sex transmission (less efficient)
66
How can HTLV-1 be transmitted within the host
Cell Associated via contact between infected and naive cells
67
What disease does HTLV-1 cause
Adult T-cell Lymphoma/Leukemia (ATLL)
| HYLV-1 Associated Myelopathy / Tropical Spastic Paraparesis (HAM/TSP)
68
what must HTLV-1 be exposed to to cause Adult T-cell Lymphoma/Leukemia
Following mucosal exposure
69
how often does HTLV-1 cause ATLL
204% of cases
70
latent period for ATLL
30-50 years
71
What does HTLV-1 infect to cause ATLL
Infect memory T-cells
72
what triggers transcription of provirus HTLV-1
Antigen activation
73
what triggers cell proliferation with HTLV-1
Virus Tax Proteins and others
74
what does HTLV-1 do with ATLL
Cell become transformed generating tumors with or without virus protein expression
75
How often does HAM/TSP occure when infected with HTLV-1
1-2% of cases
76
how would someone get HAM/TSP
following transfusions
77
what does HAM/TSP infect
T-cells
78
once HAM/TSP infects T cells what happens
enter the CNS
Activate AStrocytes, microglial cells
Recruit inflammatory cells- further tissue damage
79
when does HAM/TSP occure
3 years after infection
80
progession of HAM/TSP
starts with bladder control issues
Progress to lower back pain, leg weakness or stiffness in hip
men suffer impotence or erectile dysfunction
81
Preventing HTLV-1
eliminate breastfeeding for HTLV-1 positive moms
| INcrease screening for blood products
82
How to Treat ATLL
treat the lymphoma/leakemia with chemotherapy regardless of HTLV infections
83
how to treat HAM/TSP
Corticosteriod, interferon yielding temporary relief of symtpoms
84
types of HIV in humans
type 1 and type 2
85
type of Virus is HIV
Lentivirus
86
how was HIV discovered
due to immune deficiency occurring in previously healthy young gay men in 1984
87
who is most likely to get HIV
Homosexuals
Injection drug users
Hemophiliacs
Transfusion recipients
88
extent of HIV
World wide pandemic with significant impact
89
how bad is HIV in sub-saharan africa
it really is decreasing life expectancy
90
first drug to fight aids
AZT
91
what does AZT target as an aids med
reverse transcriptase
92
HIV transmission
Sex transmission (Primary route)
Parenteral
mother to infant
93
odds of getting HIV in sex
Female to male: 1:600-1:3000
Male to female - 1:200 - 1:2000
Male to Male - 1:10 to 1:1600
94
odds of getting HIV parenterally
Transfusion - 95%
| needle sharing - 1:150
95
odds of getting HIV from mom to infant
No AZT - 1:4
| AZT - less than 1:10
96
Latent period for AIDS
6 months to 25 years
97
How does HIV infection begin
Begins in virus containing blood or body fluid to a mucosal surface or blood
98
what does HIV target
memory T-cells (CD4+)
99
when does Acute infection with HIV occure
2 weeks aftetr infection
100
signs of HIV infection
Mucocutaneous ulceration and weight loss
101
what is seeded as a rusult of an acute infection (reservoir)
GALT
102
Rounds of infection in GALT
```
1st Primary infection where it accutely affects the T cell population
dormancy
T cells eventually begin to drop
Constituional symptoms
Opportunistic disease
Death
```
103
Common Opportuistic infections due to HIV
```
CAndida
Coccidioidomycosis
Cryptococcus
Cytomegalovirus
Kaposi
sarcoma
Tuberculosis
Taxoplasmosis
Wasting due to HIV infection
```
104
Prevention of HIV
sex behavior and protection
| Blood screening
105
Treating HIV
No vaccine
| Antiviral treatments
106
what antivirals are used to treat HIV
Nuceloside reverse transcriptase inhibitors (NRTI)- azidothymidine (AZT)
Protease Inhibitors - Ritonavir
Non-nucleoside RT inhibitors (NNRTI) - Efavirenz
Highly Active Antiretroviral Therapy (HAART) - combines 3 of the treatment options
