Brodard, V

Depatureaux, A

Lemee, V

Leoz, M

Plantier, J,

Strady, C.

Vessiere, A

English

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HAL Id: hal-02264822
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First Evidence of a HIV-1 M/O Recombinant Form
Circulating Outside Cameroon
M Leoz, A Vessiere, V Brodard, C. Strady, A Depatureaux, V Lemee, J
Plantier
To cite this version:
M Leoz, A Vessiere, V Brodard, C. Strady, A Depatureaux, et al.. First Evidence of a HIV-1 M/O Re-
combinant Form Circulating Outside Cameroon. CROI, Feb 2009, Montreal, Canada. ￿hal-02264822￿
First Evidence of a HIV-1 M/O Recombinant Form 
Circulating Outside Cameroon
M Leoz1, A Vessiere2, V Brodard3, C Strady3, A. Depatureaux1, V Lemee1, JC Plantier1
1CHU Charles Nicolle, Rouen, France, 2Centre Pasteur du Cameroun, Yaoundé, Cameroun, 
3CHU Robert Debré, Reims, France 
Table 1: Viral loads, serotyping and group-specific 
amplifications results. Group O specific results are 
indicated in red, group M specific in green, and non 
specific in blue. 
Figure 3: Phylogenetic analysis of the integrase region (a) and the vpr 
to gp120 region (b) of the RBF209 isolate together with the three 
previously described M/O recombinant forms. Method: Neighbor-
Joining (1000 bootstraps tests), Distances Calculation: Kimura-2-
Parameters model   
 O.SN.99.SEMP1299
 O.SN.99.SEMP1300
 Peeters 97CA MP645M O
 O.CM.99.99CMU4122
 O.CM.x.pCMO2 3
 O.CM.98.98CMU5337
 O.CM.98.98CMU2901
 O.US.97.97US08692A
 O.CM.98.98CMABB141
 O.CM.98.98CMABB197
 O.CM.98.98CMA105
 O.BE.87.ANT70
 O.CM.98.98CMA104
 O.CM.96.96CMA102
 O.CM.97.97CMABB497
 O.CM.96.96CMABB637
 O.CM.97.97CMABB447
 O.FR.92.VAU
 O.CM.96.96CMABB009
 O.CM.98.98CMABB212
 O.CM.91.MVP5180
 RBF209
 D.CM.01.01CM 0009BBY
 Takehisa.CMR709 49
 Takehisa.CMR709 55
 B.FR.83.HXB2-LAI-IIIB-BRU
 D.CD.NDK
 C.IN.95IN21068
 H.CF.90CF056
 F1.FR.MP411
 K.CD.EQTB11C
 J.SE.SE7887
 G.NG.92NG083
 A1.KE.Q23-17
 02 AG.NG.IBNG
 Yamaguchi.DSC1320
 Takehisa.CMR709 34
 Takehisa.95CM61 56
 Takehisa.CMR709 2098
100
99
100
99
100
100
92
64
91
45
37
22
45
29
49
100
100
100
100
100
95
100
87
100
84
100
39
50
51
66
64
79
82
58
72
0.05
HIV-O
HIV-M
(b)(a)
0.02
O.SN.99.SEMP1299
O.SN.99.SEMP1300
O.CM.99.99CMU4122
O.CM.98.98CMU2901
O.CM.98.98CMU5337
O.CM.x.pCMO2 3
RBF209
O.BE.87.ANT70
O.US.97.97US08692A
O.CM.98.98CMABB141
O.CM.98.98CMABB197
O.CM.98.98CMA105
O.CM.96.96CMABB637
O.CM.97.97CMABB447
O.CM.98.98CMA104
Yamaguchi.DSC1320
O.CM.96.96CMA102
O.CM.97.97CMABB497
Takehisa.CMR709 55
Takehisa.95CM61 56
Takehisa.CMR709 49
Takehisa.CMR709 20
Takehisa.CMR709 34
O.FR.92.VAU
O.CM.96.96CMABB009
O.CM.98.98CMABB212
O.CM.91.MVP5180
H.CF.90CF056
02 AG.NG.IBNG
Peeters 97CA MP645M O
G.NG.92NG083
A1.KE.Q23-17
C.IN.95IN21068
D.CM.01.01CM 0009BBY
D.CD.NDK
B.FR.83.HXB2-LAI-IIIB-BRU
F1.FR.MP411
J.SE.SE7887
K.CD.EQTB11C
97
42
70
88
31
23
28
25
20
41
99
75
34
68
99
98
54
66
92
41
99
26
82
4542
23
79
47
31
69
43 41
25
23
28
64
HIV-O
HIV-M
REFERENCES:
[1] Takehisa et al; Human Immunodeficiency Virus Type 1 Intergroup (M/O) Recombination in Cameroon. J. Virol 1999; 73:6810-6820
[2] Peeters et al; Characterization of a Highly Replicative Intergroup M/O Human Immunodeficiency Virus Type 1 Recombinant Isolated from a Cameroonian 
Patient. J.Virol 1999; 73:7368-7375
[3] Yamaguchi et al; HIV Infections in Northwestern Cameroon: Identification of a HIV Type 1 Group O and Dual HIV Type Group M and Group O Infections. 
AIDS Res. and Hum. Retroviruses 2004; 20:944-957
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Roche Taqman <1,6
Abbott M2000 4,8
in house LTRO 4,1
in house intO 5,0
Serotyping PLIA HIV-M
VIH-O + + + -
VIH-M - - - -
Viral Loads 
(log)
Group-Specific 
Amplification
Figure 1:Optical densities observed using IDR peptides 
(a) or V3 peptides (b) of various HIV types and groups
RESULTS:
The viral loads results were firstly in favour of a group O
infection. The HIV-M specific Roche Cobas Taqman test was
undetectable while the HIV-O specific methods were positive
as the non specific Abbott M2000 (tab.1). However,
serotyping clearly indicated a specific group M reactivity
(fig1).
Group specific amplifications were positive only for HIV-O in
the pol gene, and surprisingly no group-specific amplification
was positive in the gp41 region (tab.1).
The near full length sequencing of the circulating viral RNA
revealed a O-M-O recombinant form (fig.2) with a breakpoint
in the gp41 region, explaining the negative results with group-
specific primers. Another breakpoint was located on the first
codon of vpr, where two of the three previously described
M/O recombinants already shown a group switch.
Phylogenetic analyses indicated that RBF209 was not linked
to the other M/O recombinants (fig.3).
The absence of HIV-O specific antibodies (fig.1) together with
the negativity of group M specific PCR in the pol gene and no
amplication of M or O in the gp41, suggest that this young
patient does not carry the parental HIV-O and HIV-M strains.
Figure 2: Characterization of the near full lenght O-M-O recombinant 
form. (a) Similarity plot indicating a HIV-O / HIV-M subtype D / HIV-
O structure; (b) mapping the breakpoints on HIV-1 genome; (c) 
evidence of O/M recombination on the firs codon of vpr  
(b)
(a)
(c)
CONCLUSION:
This fourth intergroup M/O recombinant form is the first
described outside Cameroon.
Unlike the previously described cases witch emerged during
a co-infection, this could be the first direct transmission by
a M/O recombinant form ever described, emphasizing the
dynamic and a possible spread of such strains.
This kind of genome structure has consequences for the
follow up and treatment of the patient, as there are HIV-O
related mutations in the pol-encoding protease, RT and
integrase, but targets of the entry inhibitors are HIV-M.
With three intergroup recombinants switching in the vpr
gene and the fourth at the end of the integrase, the
hypothesis of a hotspot of intergroup recombination in
vpr or around the accessory genes region has to be explored.
INTRODUCTION:
HIV-O infection is endemic in Cameroon. Among these patients HIV-O
positive (= 1% of all HIV infections), seroprevalence studies showed at least
10% of HIV-M/HIV-O dual infections, but only three O/M recombinant forms
have been previously described [1, 2, 3].
In France, 119 patients have been yet identified with HIV-O infection, most of
them originating from Cameroon. The suspicion of HIV-O infection often
comes on the occasion of diagnosis difficulties or virological-clinical
discordances due to their high genetic divergence compared to HIV-M, which
can lead to poor or total lack of detection by certain commercial tests.
Complementary analyses were
performed using :
- in-house HIV-O specific
viral loads, targeting the LTR
and integrase regions
-serotyping assay using
peptides that mimic the
Immuno-Dominant Region
(IDR) of the gp41 and the V3
loop of the gp120 specific to
HIV-1 groups M, N and O and
HIV-2
- HIV-O or M group-specific
PCR in the Protease, Reverse
Transcriptase (RT), Integrase
and Gp41 regions
- near full-lengh genome
characterization from viral
RNA and intracellular DNA,
using non specific XL-RT-
PCR and XL-PCR, and
sequencing with a set of 37
primers.
PATIENTS AND METHODS:
A 25years old Cameroonian woman (RBF209) living in France since 2000
had consulted at the Universitary Hospital of Reims (eastern France) in
May 2008. Her biological and virological analyses indicated (tab.1):
-CD4 = 6/mm3
- viral load = undetectable (Roche Cobas Taqman)
- viral load = 6.104 cop/ml (Abbott Realtime)
Equipe d’accueil EA2656
Faculté de Médecine - Pharmacie
Université de Rouen
Pôle Biologie
Unité de Virologie
Hôpital Ch. Nicolle
CHU de Rouen
Mailing:
Jean-Christophe PLANTIER
Unité de Virologie - Institut de Biologie Clinique
CHU Charles Nicolle
1 rue Germont
76000 Rouen – FRANCE
E-mail: 
jean-christophe.plantier@univ-rouen.fr
Tel:
(+33) 2 32 88 82 36
Fax:
(+33) 2 32 88 04 30
AKNOWLEDGEMENTS:
Laboratorie associé au 
Centre National de Référence VIH
Agence Nationale de Recherche
sur le SIDA et les hépatites virales


First Evidence of a HIV-1 M/O Recombinant Form Circulating Outside Cameroon

https://hal-normandie-univ.archives-ouvertes.fr/hal-02264822/file/CROI%202009%20poster%20Recombinant%20MO.pdf

First Evidence of a HIV-1 M/O Recombinant Form Circulating Outside Cameroon

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