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The presence of the Y181C mutation in HIV-1 group O strains is clade dependant
M Leoz, F de Oliveira, A Kfutwah, A Vessiere, A Depatureaux, F Damond, J.C. Plantier
To cite this version:
M Leoz, F de Oliveira, A Kfutwah, A Vessiere, A Depatureaux, et al.. The presence of the Y181C
mutation in HIV-1 group O strains is clade dependant. 16th International Bioinformatics Workshop on
virus evolution and molecular epidemiology, Aug 2010, Baltimore, MD, United States. �hal-02272178�
BACKGROUND
Human Immunodeficiency Virus type 1 group O (for outlier, HIV-O) has emerged at about the same time as group M (for major, HIV-M), but remains endemic in Cameroon while HIV-M has became pandemic. The very localized diversification of HIV-O has resulted in a “comet-like”
phylogenetic structure very different from the double star characterizing the HIV-M phylogeny. Two HIV-O classifications have been proposed on the basis of relatively few sequences, identifying five and three clades respectively, and both shown a disproportion with a majority of strains falling into clade I (Yamaguchi 2002) or A (Roques 2002) (fig.1).
METHODS
136 samples from HIV-O infected NNRTI-naïve patients from France (n=
74) and Cameroon (n= 62) have been used for viral RNA extraction, amplification and sequencing in the protease and partial RT regions, phylogenetic analysis and Y181C mutation search.
RESULTS
Among the 136 strains, only 76 harbour a Y181C mutation, 93% of which belonging to cluster A, while Y181Y is found in 91% of the non-A strains (fig.2). One virus (0.8%) harbored a mixture Y181Y/C on sequential samples (RBF165).
Interestingly, the sub-clade A3, together with a cluster of sequences associated to A3 in this region (indicated with a star in both figures), but not in the gp41, show a 181Y residue for 24 sequences out of 26.
Note that the branching of the sub-clade A2 is different from the one observed in the gp41 region.
The presence of the Y181C mutation in HIV-1 group O strains
is clade dependant
Leoz M. (*1), de Oliveira F. (1), Kfutwah A (2), Vessière A (1,2), Depatureaux A (1), Damond F. (3), Plantier JC (1)
1
Laboratoire associé au Centre National de Référence du VIH, EA2656, CHU Charles Nicolle, Rouen, France
2
Laboratoire de Virologie, Centre Pasteur du Cameroun, Yaoundé, Cameroun
3
Laboratoire de Virologie, hôpital Bichat, AP-HP, Paris, France
CHU Charles Nicolle de RouenLaboratoire de Virologie
Faculté de Médecine-Pharmacie Université de Rouen GRAM EA2656 IHURBM IFRMP23
Laboratoire associé au Centre National De Référence VIH
Most of the HIV-O strains are know to harbor a Y181C mutation in the Reverse Transcriptase (RT), leading to a possible natural resistance to the Non Nucleoside RT Inhibitors (NNRTIs); here we investigate the relationship between the presence of this mutation and the phylogenetic classification of HIV-O strains.
CONCLUSION
The wide diversity of group O viruses is still difficult to explore since it has resulted from a very localized evolution. As a consequence, there are only few and weakly defined clusters, and many strains remain unclassified, but some clusters (as AI/Ib and A3/U) become significant with the contribution of new sequences.
Despite the dichotomy between a major “clade” A and the other sequences, we show that A3 can share some characteristics with non-A sequences, and interestingly, 97CMABB497, the only sequence belonging to this cluster which appeared in Yamaguchi's analysis and remained unclassified, could be of recombinant origin (Yamaguchi 2003). Moreover, the cluster A2 and another unclassified cluster from the major clade show evidences of recombination.
Further investigations, using more tools and larger sets of sequences in different regions of the genome, are needed to better understand the evolution of HIV-O and possibly define a relevant nomenclature.
Fig.1: Phylogenetic analysis of 256 HIV-O partial gp41 sequences.
Sequences were aligned using MEGA.4 and manually edited when needed; 525 positions remained after removing those who could not be aligned unambiguously.
Tree reconstruction was inferred using the Neighbor Joining method, and Tamura-Nei estimated distances using G - distributed rates along sites with parameter a =0,33.
Fig.1: Phylogenetic analysis of 136 HIV-O partial pol sequences (987 positions encompassing the full protease and 230 codons of the RT) . Sequences were aligned using MEGA.4. Tree reconstruction was inferred using the Neighbor Joining method and Tamura-Nei estimated distances using G -distributed rates along sites with parameter a =0,25.
BCF005 RBF152
BCF155 BCF181
YBF256 YBF289 YBF240
YBF279
RBF142 RBF194 RBYYFB164BF016F209
RBF210RBF209
B CF159 BCF171 BCF014 YBF261 BCF173 BCF109
BBCFC007F120 YBF241 BCF112YBF263
RBF151 BCF002 RBF201 YBF231YBF224YBF276 RBF157YBF264YBF227 YBF257RBF147YBF274BCF045YBF026RBF165YBF278RBF146YBF233RBF208RBF145RBF166BCF108
BCF192BCF185BCF176 B CF004 RBF153
YBF236 BC
F107BCF008 YBF220RB
F170YBF032 BC
F191
BC F178 YBF
260
YB F015 YB
F271 BC
F099 BC F100
YB F038 BCF 124
BCF001RBF130BCF158 BCF
113
BCF
114
YB
F211
CB 101F
CB
183FB
FC
111 BR
137 F CB F118 YBF305
YBF306YBF307YBF247
YBF018 BCF003
YBF203 YBF230
RBF189 RBF190
YBF268 YBF293
YBF270 YBF245
YBF213 BCF188
BCF174 YBF204YBF251YBF269 BCF123
YBF039 YBF200YBF216 RBF156YBF222 YBF210 YBF208
YBYF232B F235 YBF056
RB F128 YB
F234 YB YBFYF212017B
F267
BCF011
YB F202 RBF129 YB
F250
RBF140 YB
F035
BC F160 RB
F206
YB F243Y
BF 244 BC
F006
BCF
058
YBF226
BCF057RBF125
YBF037BCF175
RBF169
0.02
Non-A C
B A
A2 A1 A3
Classification from Roques et al
C/ III
B/ II V
A3 A2 /IV A1/Iu A1/Iu
A1/Ib
97CMABB497 A1/Ia
