Chaix, M,

Delaugerre, C.

Leoz, M

Meyer, L

Plantier, J,

Rivoisy, C

Rouzioux, C

Simon, F

Chaix, M, L

Plantier, J, C

HAL UVSQ

Circulation of Multiple Patterns of Unique Recombinant Forms B/CRF02_AG in France

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Circulation of Multiple Patterns of Unique Recombinant
Forms B/CRF02_AG in France
M Leoz, M Chaix, C. Delaugerre, C Rivoisy, L Meyer, C Rouzioux, F Simon,
J Plantier
To cite this version:
M Leoz, M Chaix, C. Delaugerre, C Rivoisy, L Meyer, et al.. Circulation of Multiple Patterns of
Unique Recombinant Forms B/CRF02_AG in France. HIV Dynamics and Evolution, 2011, Galway,
Ireland. ￿hal-02272128￿
Circulation of Multiple Patterns of Unique Recombinant Forms B/CRF02_AG in France
Precursor Signs of the Emergence of an Upcoming Circulating Recombinant Form CRF_B/02_AG?
M LEOZ1,2, ML CHAIX3, C DELAUGERRE4, C RIVOISY3, L MEYER5, 
C ROUZIOUX3, F SIMON4, JC PLANTIER1,2
1Laboratoire associé au CNR VIH, CHU Charles Nicolle, Rouen, France ; 
²GRAM EA 2656, Faculté de Médecine-Pharmacie, université de Rouen, Rouen, France ; 
3Université Paris Descartes, Faculté de Médecine, EA 3620, Paris AP-HP, Laboratoire de Virologie, CHU Necker-Enfants malades, Paris, France; 
4 Laboratoire de Virologie, CHU Saint Louis, Paris, France
5 INSERM U1018, Université Paris Sud, Faculté de Médecine Paris Sud, AP-HP, Le Kremlin Bicêtre, France
AIDS 2011, in press
Fig.1: evolution of the proportion of non-B strains 
among primo-infections in France 
(adapted from Chaix et al, 2009)
CHU Charles Nicolle de Rouen
Laboratoire de Virologie
Faculté de 
Médecine-Pharmacie
Université de Rouen
GRAM EA2656 
IHURBM
IFRMP23
Laboratoire associé
au Centre National
De Référence VIH
In France, the epidemic is 
characterised by :
-predominance of subtype B strains,
- increasing prevalence of non-B 
subtypes (fig.1), CRF02_AG being 
the most prevalent,
- increasing at-risk behaviour in the 
MSM population. 
Travaux soutenus par 
l’Agence Nationale de 
Recherche contre le SIDA
0%
5%
10%
15%
20%
25%
30%
[1
99
6 
- 1
99
8]
[1
99
9 
- 2
00
0]
[2
00
1 
- 2
00
2]
[2
00
3 
- 2
00
4]
[2
00
5 
- 2
00
6]
year of diagnostic
p
ro
p
o
rt
io
n
 o
f 
n
o
n
-B
total
MSM
BACKGROUND
HIV-1 group M is characterised by substantial genetic diversity, and includes 
nine subtypes, more than 45 CRFs, and numerous Unique Recombinant 
Forms (URFs). 
The high prevalence and co-circulation of B and CRF02_AG strains in this 
population raise the possibility that recombinant forms might emerge and spread. 
METHODS
RESULTS
Seven samples were selected from seven patients, of whom five are MSM (tab.1)
patient sex
age 
(years) origin risk group
year of diagnosis of 
HIV infection  year of sampling therapeutic status
CD4 
(cells/mm3) 
RNA viral 
load Log 
copies/mL
URF
b
 and 
size (bp)
nb of SGA 
sequences
c 
P1 M 67
France 
(caucasian)  homosexual 2008 2008 naive 490 5.8 URF1 : 8659 8
P2 F 46
France 
(caucasian)  IDU 2004 2009 naive 504 3.7 URF2 : 8891 11
P3 M 38
France 
(caucasian)  homosexual 2006 2009 treated 549 5 URF3 : 8295 8
P4 M -
a
-
a
-
a
2002 2002 -
a
-
a
5.1 URF4 : 8424 10
P5 M 25
France 
(caucasian)  homosexual 2010 2010 naive 159 5.1 URF5 : 8396 10
P6 M 39
France 
(caucasian)  homosexual 2006 2006 naive 391  5.2 URF6 : 9608 NA
P7 M 32
France 
(caucasian)  homosexual 2006 2006 naive 397 6.2 URF7 : 9158 NA
a
: not available
b
: URF identified in the patient
c
: number for a given URF of sequences obtained by SGA for breakpoint confirmation
NA: not applicable
Tab.1: Characteristics of the seven patients from whom the samples were selected, and of the 
corresponding URFs characterized
Two of the seven new URFs 
involve a 3rd subtype (fig. 
2.a).
The seven recombination 
patterns are distinct from 
each other (fig. 2.a), and 
from the only two 
previously described 
B/CRF02 URFs from 
Cyprus (Kousiappa et al., 2009) 
and Spain (Holguin et al., 
2008).
The breakpoints are 
distributed all along the 
genome (fig. 2.b) with 
hotspots in pol at the 
protease-to-Reverse 
Transcriptase border, and in 
vpu where the overlapping 
start of env is located.
Refs B
Refs 02
Fig.2: Recombination patterns of the 7 new URFs and the 2 previously described (a) and 
breakpoints distribution along the genome (b)
Fig.3: Example of SGA results for URF2. The 11 sequences obtained are aligned with a set of 
subtype B (blue box) and CRF02 (red box) reference sequences to determine their recombination 
patterns; the yellow box indicates the region were recombination occured for these SGA sequences. 
There was no evidence of parental or minor recombinant strains circulation, although 
polymorphism was observed for all the strains tested (fig. 3). 
URF1
FJ388896
(Cyprus)
DQ926899
(Spain)
a)
URF2
URF3
URF4
URF5
URF6
URF7
b)
Fig.4: Phylogenetic network 
representing the relationships 
between the env gp120 sequences of 
the 9 URFs and a set of reference 
sequences.
In the env gp120 region, URF3 
and URF7 appeared to be linked 
despite their different 
recombination patterns. 
No link was observed between 
any URF in the pol pr-RT region 
(not shown)
CONCLUSIONS
The complexity of the molecular epidemiology is growing in France due to the raise of non-B strains prevalence and to subsequent recombinations
The predominant forms, subtype B and CRF02, are co-circulating in the MSM population and frequent co-infections led to local emergence of several URFs, 
one of those (URF7) being linked with a cluster of CRF02_AG sequences identified in the MSM population of Paris
The absence of parental strains suggests direct transmission of these strains, indicating that they could spread in particular within this population
A surveillance is needed to determine if this dynamic could lead to the genesis of a new CRF_B/CRF02_AG in France
Screening for subtyping discordances in different regions of the genome
Near full length sequencing and pattern characterization
Searching for parental strains or minor recombinants using Single Genome Analysis
Analysis of the phylogenetic relationships between the B/CRF02 recombinants


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Circulation of Multiple Patterns of Unique Recombinant Forms B/CRF02_AG in France

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