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New and old complex recombinant HIV-1 strains among patients with primary infection in 1996-2006 in France: the French ANRS CO06 primo cohort study.

Frange P, Galimand J, Vidal N, Goujard C, Deveau C, Souala F, Peeters M, Meyer L, Rouzioux C, Chaix ML - Retrovirology (2008)

Bottom Line: Others PHI were further observed in 2006-2007 with 1 KZS and 5 CRN-like viruses, suggesting their spread in France.This study illustrates the increasing HIV-1 diversity in France associating new (06FR-CRN) and old (CRF27_cpx and "MAL-like" 04FR-AUK) strains, which are rare in their region of origin but may have a possible founder effect in France.Our results strengthen the French guidelines recommending viro-epidemiological surveillance of HIV-1 diversity.

View Article: PubMed Central - HTML - PubMed

Affiliation: EA 3620, Université Paris - Descartes, Laboratoire de Virologie, Hôpital Necker - Enfants Malades, AP-HP, Paris, France. pierre.frange@nck.aphp.fr

ABSTRACT

Background: Prevalence of HIV-1 non-B subtypes has increased overtime in patients diagnosed at the time of primary infection (PHI) in France. Our objective was to characterize in detail non-B strains which could not be genetically classified into the known subtypes/Circulating Recombinant Forms (CRFs).

Methods: Among 744 patients enrolled in the ANRS PRIMO Cohort since 1996, 176 (23.7%) were infected with HIV-1 non-B strains. The subtype/CRF could not be identified in RT for 15 (2%). The V3-V5 env region was sequenced and 3 strains (04FR-KZS, 06FR-CRN, 04FR-AUK) were full-length sequenced. Phylogenetic and bootscan analyses were used to characterize the mosaic structures.

Results: Among V3-V5 sequences, 6 were divergent A, 2 distantly related to E or D, 2 C, 1 B and 2 remained unclassified. 04FR-KZS, isolated in a Congolese woman infected in France, clustered with 2 previously described viruses from the Democratic Republic of Congo. They represent CRF27_cpx involving A/E/G/H/J/K/U subtypes. 06FR-CRN, isolated in a homosexual Caucasian patient, was a B/C/U recombinant involving a Brazilian C strain. 04FR-AUK, isolated in a Congolese patient infected in France, was a A/K/CRF09/U recombinant clustering from gag to vif with HIV-1 MAL. Others PHI were further observed in 2006-2007 with 1 KZS and 5 CRN-like viruses, suggesting their spread in France.

Conclusion: This study illustrates the increasing HIV-1 diversity in France associating new (06FR-CRN) and old (CRF27_cpx and "MAL-like" 04FR-AUK) strains, which are rare in their region of origin but may have a possible founder effect in France. Our results strengthen the French guidelines recommending viro-epidemiological surveillance of HIV-1 diversity.

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Phylogenetic tree analysis of the 15 "undetermined" viruses isolated in patients enrolled at the time of primary infection. In the phylogenetic trees, based on the RT nucleotide sequence of the 15 “undetermined” strains (a) and the corresponding V3-V5 env region for 13 of them (b), the reference sequences were as follows: 3 references for all pure subtypes, 1 reference for 18 previously described CRF (CRF01-16 and CRF18-19), and unique recombinant MAL [23], NOGIL [24] and 97CD-KTB49 [18] strains. Trees based on unambiguously aligned nucleotides were generated by the neighbour-joining method, and the reliability of each clustering was assessed by bootstrapping with one hundred replicates implemented by Clustal W. The Simplot v3.5.1 performed bootscanning on NJ trees along the genome alignment by moving a 400 base pairs window along the genome alignment with 20 base pairs increment and one hundred replicates for each phylogeny. Only bootstrap values above 70 at each of the internal branches defining a subtype are shown.
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Figure 1: Phylogenetic tree analysis of the 15 "undetermined" viruses isolated in patients enrolled at the time of primary infection. In the phylogenetic trees, based on the RT nucleotide sequence of the 15 “undetermined” strains (a) and the corresponding V3-V5 env region for 13 of them (b), the reference sequences were as follows: 3 references for all pure subtypes, 1 reference for 18 previously described CRF (CRF01-16 and CRF18-19), and unique recombinant MAL [23], NOGIL [24] and 97CD-KTB49 [18] strains. Trees based on unambiguously aligned nucleotides were generated by the neighbour-joining method, and the reliability of each clustering was assessed by bootstrapping with one hundred replicates implemented by Clustal W. The Simplot v3.5.1 performed bootscanning on NJ trees along the genome alignment by moving a 400 base pairs window along the genome alignment with 20 base pairs increment and one hundred replicates for each phylogeny. Only bootstrap values above 70 at each of the internal branches defining a subtype are shown.

Mentions: From 1996 to October 2006, 744 strains have been genetically characterized among the 768 patients recruited in the PRIMO cohort. Phylogenetic analysis revealed that 176 (23.7%) were HIV-1 non-B strains. Whereas the majority of them (57%) were CRF02_AG viruses [11], 15 (2%) were not classified into the known HIV-1 subtypes or CRFs (Figure 1a). The clinical, virological and immunological characteristics of the 15 patients at the time of their inclusion in the cohort are summarized in the Table 1. Among the 15 strains, two clusters of very closely related strains (> 99% homology) were identified: 03FR-ATKL and 03FR-JHW from 2 heterosexual partners, and 06FR-CRN and 06FR-ETU among two men having sex with men (MSM) whose PHI occurred in 2006, although diagnosed in two different cities. V3-V5 sequences were done on the 15 unclassified samples. A total of 13 "undetermined" strains have been amplified and sequenced: 6 clustered in the subtype A radiation but did not form a well supported cluster with an A sub-subtype or CRF specific subtype A lineage. Two samples were distantly related to subtype E or D, 2 could be classified as C, 1 as B and 2 remained undetermined (Figure 1b).


New and old complex recombinant HIV-1 strains among patients with primary infection in 1996-2006 in France: the French ANRS CO06 primo cohort study.

Frange P, Galimand J, Vidal N, Goujard C, Deveau C, Souala F, Peeters M, Meyer L, Rouzioux C, Chaix ML - Retrovirology (2008)

Phylogenetic tree analysis of the 15 "undetermined" viruses isolated in patients enrolled at the time of primary infection. In the phylogenetic trees, based on the RT nucleotide sequence of the 15 “undetermined” strains (a) and the corresponding V3-V5 env region for 13 of them (b), the reference sequences were as follows: 3 references for all pure subtypes, 1 reference for 18 previously described CRF (CRF01-16 and CRF18-19), and unique recombinant MAL [23], NOGIL [24] and 97CD-KTB49 [18] strains. Trees based on unambiguously aligned nucleotides were generated by the neighbour-joining method, and the reliability of each clustering was assessed by bootstrapping with one hundred replicates implemented by Clustal W. The Simplot v3.5.1 performed bootscanning on NJ trees along the genome alignment by moving a 400 base pairs window along the genome alignment with 20 base pairs increment and one hundred replicates for each phylogeny. Only bootstrap values above 70 at each of the internal branches defining a subtype are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2553414&req=5

Figure 1: Phylogenetic tree analysis of the 15 "undetermined" viruses isolated in patients enrolled at the time of primary infection. In the phylogenetic trees, based on the RT nucleotide sequence of the 15 “undetermined” strains (a) and the corresponding V3-V5 env region for 13 of them (b), the reference sequences were as follows: 3 references for all pure subtypes, 1 reference for 18 previously described CRF (CRF01-16 and CRF18-19), and unique recombinant MAL [23], NOGIL [24] and 97CD-KTB49 [18] strains. Trees based on unambiguously aligned nucleotides were generated by the neighbour-joining method, and the reliability of each clustering was assessed by bootstrapping with one hundred replicates implemented by Clustal W. The Simplot v3.5.1 performed bootscanning on NJ trees along the genome alignment by moving a 400 base pairs window along the genome alignment with 20 base pairs increment and one hundred replicates for each phylogeny. Only bootstrap values above 70 at each of the internal branches defining a subtype are shown.
Mentions: From 1996 to October 2006, 744 strains have been genetically characterized among the 768 patients recruited in the PRIMO cohort. Phylogenetic analysis revealed that 176 (23.7%) were HIV-1 non-B strains. Whereas the majority of them (57%) were CRF02_AG viruses [11], 15 (2%) were not classified into the known HIV-1 subtypes or CRFs (Figure 1a). The clinical, virological and immunological characteristics of the 15 patients at the time of their inclusion in the cohort are summarized in the Table 1. Among the 15 strains, two clusters of very closely related strains (> 99% homology) were identified: 03FR-ATKL and 03FR-JHW from 2 heterosexual partners, and 06FR-CRN and 06FR-ETU among two men having sex with men (MSM) whose PHI occurred in 2006, although diagnosed in two different cities. V3-V5 sequences were done on the 15 unclassified samples. A total of 13 "undetermined" strains have been amplified and sequenced: 6 clustered in the subtype A radiation but did not form a well supported cluster with an A sub-subtype or CRF specific subtype A lineage. Two samples were distantly related to subtype E or D, 2 could be classified as C, 1 as B and 2 remained undetermined (Figure 1b).

Bottom Line: Others PHI were further observed in 2006-2007 with 1 KZS and 5 CRN-like viruses, suggesting their spread in France.This study illustrates the increasing HIV-1 diversity in France associating new (06FR-CRN) and old (CRF27_cpx and "MAL-like" 04FR-AUK) strains, which are rare in their region of origin but may have a possible founder effect in France.Our results strengthen the French guidelines recommending viro-epidemiological surveillance of HIV-1 diversity.

View Article: PubMed Central - HTML - PubMed

Affiliation: EA 3620, Université Paris - Descartes, Laboratoire de Virologie, Hôpital Necker - Enfants Malades, AP-HP, Paris, France. pierre.frange@nck.aphp.fr

ABSTRACT

Background: Prevalence of HIV-1 non-B subtypes has increased overtime in patients diagnosed at the time of primary infection (PHI) in France. Our objective was to characterize in detail non-B strains which could not be genetically classified into the known subtypes/Circulating Recombinant Forms (CRFs).

Methods: Among 744 patients enrolled in the ANRS PRIMO Cohort since 1996, 176 (23.7%) were infected with HIV-1 non-B strains. The subtype/CRF could not be identified in RT for 15 (2%). The V3-V5 env region was sequenced and 3 strains (04FR-KZS, 06FR-CRN, 04FR-AUK) were full-length sequenced. Phylogenetic and bootscan analyses were used to characterize the mosaic structures.

Results: Among V3-V5 sequences, 6 were divergent A, 2 distantly related to E or D, 2 C, 1 B and 2 remained unclassified. 04FR-KZS, isolated in a Congolese woman infected in France, clustered with 2 previously described viruses from the Democratic Republic of Congo. They represent CRF27_cpx involving A/E/G/H/J/K/U subtypes. 06FR-CRN, isolated in a homosexual Caucasian patient, was a B/C/U recombinant involving a Brazilian C strain. 04FR-AUK, isolated in a Congolese patient infected in France, was a A/K/CRF09/U recombinant clustering from gag to vif with HIV-1 MAL. Others PHI were further observed in 2006-2007 with 1 KZS and 5 CRN-like viruses, suggesting their spread in France.

Conclusion: This study illustrates the increasing HIV-1 diversity in France associating new (06FR-CRN) and old (CRF27_cpx and "MAL-like" 04FR-AUK) strains, which are rare in their region of origin but may have a possible founder effect in France. Our results strengthen the French guidelines recommending viro-epidemiological surveillance of HIV-1 diversity.

Show MeSH
Related in: MedlinePlus