Hiv and Aids: Viral Life Cycle

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VIRAL LIFE CYCLE:


viral gp120 binds CD4 on cell surface viral gp120 conformational change altered viral
gp120 binds coreceptor CXCR4 (for T cell infection only) or CCR5 (for T cell or macrophage
infection) viral gp41 brought close to cell membrane viral gp41 mediates viruscell fusion
viral genome uncoated reverse transcriptase converts viral RNA genome to dsDNA integrase
inserts randomly several copies of dsDNA into host genome integrated provirus remains latent
when host cell activated (e.g., via chemokines), provirus genes expressed:
gag encodes polyprotein of virion core
pol encodes polyprotein of reverse transcriptase, integrase, and protease
env encodes envelope glycoproteins
six other genes encode for regulators of gene expression
viral protease cleaves polyproteins infectious particles assemble at cell membrane and bud off
cell membrane
COURSE OF CD4 T CELL COUNT AND VIREMIA:
1 Infection Stage (frst months): acute viremia contained by vigorous host immune
response mononucleosis-like symptoms equilibrium established between viral production
and host containment
Clinical Latency Stage (710 years): virus replicates, especially in lymphoid organs host
responds to contain infection, mutations allow virus to evade no or low-level symptoms
viral load gradually increases, CD4 count gradually drops
CD4 cells depleted by various mechanisms, including:
immune attack on infected cells by CTLs
cell lysis from extensive viral budding
syncytium formation between infected and uninfected cells (via gp120CD4 interactions)
Advanced Disease (AIDS): CD4 T cell count, 200 cells/L common opportunistic
infections/neoplasms causing death (see card 86 for more details)
Lipid layer
gp120 (env)
gp41 (env)
gp41 mediates viral-cell
fusion and syncytia formation
gp120 binds CD4,
CXCR4, and CCR5 on
T cells and macrophages
p24 capsid (gag)
p17 matrix (gag)
Reverse
transcriptase (pol)
Integrase (pol)
Protease (pol)
RNA
0
0 3 6 9 12 1 2 3 4 5 6 7 8 9 10 11
100
200
300
400
500
600
700
800
900
1000
1100
1200
Acute viremia,
mononucleosis-like symptoms
Weeks
C
D
4

T

c
e
l
l
s
/

L
V
i
r
e
m
i
a

(
H
I
V

R
N
A

c
o
p
i
e
s
/
m
L

p
l
a
s
m
a
)
Years
Opportunistic
diseases
Death
1 Infection Clinical Latency
Advanced Disease
(AIDS)
10
8
10
7
10
6
10
5
10
4
10
3
10
2
HIV and AIDS
001-010_Harpavat_ConceptCards.indd 10 7/10/11 1:15 AM

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