Recombination in retroviruses

1
Recombination in retroviruses
Is the most frequent genomic aberration in
retroviruses In HIV, recombination has been
shown to accelerate the generation of strains
resistant to antiviral treatment At least 20
of the infectious strains of HIV are generated by
recombination
2
The retroviral life cycle
3
Double infection
4
Recombination by copy choice
How ?
5
Pause-driven copy choice
A
B
C
RT
A
B
C
6
Pause-driven copy choice
A
B
A
B
C
7
Pause-driven copy choice
A
B
A
B
C
8
Pause-driven copy choice
A
B
A
B
C
9
Pause-driven copy choice
A
B
A
B
C
10
Recombination in vitro
lac-
5
3
5
3
Homologous region
lac
Ligation to a vector restricted by BamH I and Pst
I Transformation of E.coli
11
Recombination in vitro
lac-
5
3
Donor RNA
Acceptor RNA
5
3
Homologous region
lac
12
Context effect
R
E
V
T
A
T
R
V
P
R
N
E
F
U
5
V
P
U
HIV-1 genome
G
A
G
E
N
V
U
3
R
P
O
L
V
I
F
13
Hot
Hot
14
donor
acceptor
15
The folding of the acceptor RNA determines the
frequency of recombination
16
Molecular encounters
The encounter between the nascent DNA and the
acceptor RNA is not the limiting step
17
RNA Structure driven model
A
B
C
RT
donor
acceptor
A
B
C
18
RNA Structure driven model
A
B
C
donor
acceptor
A
B
C
19
RNA Structure driven model
A
B
donor
acceptor
A
B
C
20
RNA Structure driven model
A
B
donor
Docking
acceptor
A
B
C
21
RNA Structure driven model
A
B
donor
Displacement
acceptor
A
B
C
22
Abdeladim Moumen Lucette Polomack Michel
Veron Henri Buc Matteo Negroni Institut
Pasteur, Paris
Bernard Roques Faculté de Pharmacie, Paris
Torsten Unge Uppsala University