4.38 Flashcards

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1
Q
Retroviruses
characteristics (5)
A

• Positive strand RNA viruses (5000-12000 bp)
• Enveloped
• Contain reverse transcriptase enzyme
• Cause chronic disease long after infection
• HIV (human immunodeficiency virus) is a retrovirus
that causes AIDS (acquired immunodeficiency
syndrome)

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2
Q

• Contain reverse transcriptase enzyme

A
  • Copies RNA into DNA
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3
Q

Cause chronic disease long after infection

A
  • Due to integration of viral DNA into host

chromosome

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4
Q

HIV adsorption and penetration
M tropic (initial infection):
Receptor/coreceptor:

A

cells of macrophage lineage

CD4 and CCR5

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5
Q

HIV adsorption and penetration
T tropic (later during infection):
Receptor/coreceptor:

A

T cells

CD4 and CXCR4

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6
Q

Viral ENV protein gp120

binds to

A

cellular receptor
CD4 and to coreceptor
CXCR4 or CCR5

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7
Q

Coreceptor interaction

essential for

A

gp41 contact
and viral fusion with host
cell

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8
Q

Small number of resistant people

- lack the –

A

-coreceptors

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9
Q

HIV penetration (due to membrane fusion promoted by —)

A

gp41

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10
Q

HIV genome replication

Part 1: synthesis of viral DNA copy (2)

A

Reverse transcriptase (RT) synthesizes one strand of DNA using viral RNA as
the template.
Reverse transcriptase (RT) synthesizes the other strand of DNA using the newly
created viral single DNA strand above as the template.

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11
Q

RT enzyme is the major target for — drugs

A

anti-HIV

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12
Q

RT enzyme is — prone

A

error
(1 error every 10000 nts!)
~1 error per genome

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13
Q

Part 1: synthesis of viral DNA copy
Cellular — used as
a primer by reverse
transcriptase

A

tRNA

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14
Q

Part 1: synthesis of viral DNA copy
Several steps are required to
create a double stranded
DNA copy of the

A

positivesense, single-stranded RNA

genome

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15
Q

HIV genome replication
part 2: integration of viral DNA copy into host cell genome
Promoted by viral — enzyme

A

integrase

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16
Q

HIV genome replication
part 3: transcription of integrated viral DNA copy
to create more viral RNA

A

Viral DNA is transcribed into RNA by host cell RNA polymerase II

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17
Q

HIV protein expression

and viral assembly (2)

A
Viral RNA serves as mRNA
for translation
AND
Viral RNA serves as the
viral genome that is
packaged into virions
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18
Q

Viral assembly occurs at

A

plasma membrane.

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19
Q

Virions acquire their membrane by budding of

— from the plasma membrane

A

nucleocapsids

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20
Q

Translation creates viral

A

polyproteins

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21
Q

Viral polyproteins get
cleaved to final mature
sizes by viral —

A

protease

22
Q

HIV accessory factors (2)

A

nef

vpu

23
Q

nef

A
decreases expression of MHC class I molecules on the surface of an
infected cell, preventing killing by cytotoxic T cells
24
Q

vpu

A

reduces cell surface CD4 expression and enhances viral release

25
Q

Long terminal repeats (LTRs) (2)

A
Transcriptional promoter (upstream LTR) and terminator (downstream LTR)
Promoter responds to host cell signals and can also be relatively dormant,
creating the latent state that is an important characteristic of HIV
26
Q

HIV entry (3)

A

Virus may enter through
microabrasions on mucosal surfaces
needle punctures (IV drug users)
intact mucosal surfaces

27
Q

HIV entry

Virus may enter as (2)

A

part of an infected cell (macrophage, lymphocyte, spermatozoa)
free virus

28
Q

HIV replication during the — phase of infection

after burst of viral replication that occurs during — infection

A

chronic

initial

29
Q

HIV replication during the chronic phase of infection

after burst of viral replication that occurs during initial infection (2)

A
Note initial contact is with
macrophage lineage cells.
Infect/stick to dendritic cells
transport to lymph node - contact
with CD4 T cells
DTH
30
Q

DTH=delayed-type
hypersensitivity (Type IV hyper.)
-important for controlling (2)

DTH is mediated by

A

fungal
and intracellular pathogens
(bacterial and viral)

CD4 T cells

31
Q

HIV
Neurological symptoms
basis is not well understood (2)

A
- possibly due to viral infection of
neurons
- possibly release of substances
by other cells that promote
inflammation in brain
32
Q

<— CD4 T-cell/mm3 is the

criterion for AIDS.

A

200

Patients with higher CD4 Tcell counts are also
considered to have AIDS if
they display AIDS indicator
conditions (see next slide).

33
Q

AIDS-Indicator Conditions (Centers for Disease Control) (7)

A

Candidiasis of the bronchi, trachea, or lungs
Candidiasis, esophageal
Kaposi sarcoma
Mycobacterium avium complex (MAC) or Mycobacterium kansasii, disseminated or extrapulmonary
Mycobacterium tuberculosis, pulmonary or extrapulmonary
Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
Pneumocystis jiroveci (formerly carinii) pneumonia (PCP)

34
Q

HIV

Transmission occurs by

A

direct exposure of persons bloodstream to body
fluid containing virus. HIV is found in the blood, semen, or vaginal fluid of
someone who is infected with the virus.

35
Q

HIV is not transmitted by

A
casual contact (touching, etc.) (or
even kissing, sneezing, bug bites, etc.)
36
Q

HIV
There is a risk for health care workers
but

A

transmission even through
needlestick is poor
(less than 1% of exposures show
seroconversion)

37
Q
AIDS
characteristics (2)
A

• progressive destruction of CD4+ cells leads to collapse of immune
system
• patient susceptible to opportunistic infections

38
Q

Central nervous system disease also

associated with AIDS

A

dementia

39
Q

AIDS-related cancers

A

• Kaposis sarcoma

– caused by human herpesvirus 8

40
Q

HIV
treatment involves:
– antiviral agents (3)

A
  • nucleoside analogue reverse transcriptase (RT) inhibitors
  • nonnucleoside RT inhibitors
  • protease inhibitors
  • Fusion-penetration inhibitors (target gp41)
41
Q

HIV

Prevention and control

A

• search for vaccine is ongoing

42
Q

A recombinant virus assay was used to characterize in detail neutralizing
antibody responses directed at circulating autologous HIV in plasma. Examining serial plasma specimens in a matrix format, most patients with primary HIV infection rapidly generated significant neutralizing antibody responses to early (0-39 months) viruses, Plasma virus continually and rapidly evolved to escape neutralization, indicating that neutralizing antibody exerts a level of selective pressure that has been under-appreciated based on earlier, less comprehensive characterizations. These data argue that

A

neutralizing antibody responses account for the extensive variation in the envelope gene that is observed in the early months after primary HIV infection.

43
Q

Plasmid for producing HIV virions from within cultured
cells (only the part of the plasmid encoding HIV is shown)
(4)

A
  1. HIV DNA on plasmid is transcribed into HIV RNA.
  2. HIV RNA is translated into HIV proteins, which assemble
    into nucleocapsids.
  3. HIV RNA is also packaged into the nucleocapsids.
  4. HIV virions are created when the nucleocapsids bud
    through the cell membrane.
44
Q

The HIV DNA on the plasmid lacks the envelope gene
(env), which has been replaced with a luciferase gene.
1. This allows for HIV env genes from the patient serum
samples to be used for creation of —. The
patient env genes are expressed from a second plasmid in
the cells. Because the virions contain separately supplied
env proteins they are called —.

A

HIV virons

pseudovirions

45
Q
  1. The — present within HIV is used to detect
    subsequent infection by the — produced in
    this study. If cells become infected they will express
    —, which is easily detected using a light-based
    assay
A

luciferase
pseudovirions
luciferase

46
Q

Pseudovirions created

in a

A

producer cell

47
Q

Mixing pseudovirions with patient

serum samples:

A

different combinations
of each were used, representing virus
and antibodies present at different
times in the study

48
Q

Pseudovirions unaffected by
the antibody incubation will
infect test cells. Infection is
monitored by

A

luciferase

activity.

49
Q

Pseudovirions are artificial virions containing —. In this case the envelope proteins (2) come
from viral envelope genes amplified from patient serum samples. A collection of pseudovirions was generated that represented the
HIV population present in each of the monthly serum samples taken during the 39 month study.

A

altered envelope proteins

gp41 and gp120

50
Q

HTLV

A

human T-cell lymphotropic viruses (HTLVs) -I, -II, -III, and -IV

51
Q

HTLV-I

A

causes adult T-cell leukemia and lymphoma

52
Q

HTLV-II, -III, and –IV

A

no known diseases associated with these viruses