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HIV-1 Dual Infected LTNP-EC Patients Developed an Unexpected Antibody Cross-Neutralizing Activity.

Pernas M, Sanchez-Merino V, Casado C, Merino-Mansilla A, Olivares I, Yuste E, Lopez-Galindez C - PLoS ONE (2015)

Bottom Line: Our results showed an improved neutralization breadth in DI LTNP-EC patients when compared with matched LTNP single-infected patients.We found a positive correlation between neutralization breadth and diversity within the viral quasispecies.This correlation could explain why a group of LTNP-EC patients developed a broad neutralizing response despite having undetectable levels of viremia.

View Article: PubMed Central - PubMed

Affiliation: Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III, Majadahonda, Madrid 28220, Spain.

ABSTRACT
This study evaluated the neutralization breadth in dually infected (DI) HIV-1 long-term non-progressor elite controller patients (LTNP-EC) using a representative minipanel of 6 viruses from 5 different subtypes. Our results showed an improved neutralization breadth in DI LTNP-EC patients when compared with matched LTNP single-infected patients. The role of viral diversity in neutralization was estimated with the Shannon Entropy and the p-distance in viral quasispecies. We found a positive correlation between neutralization breadth and diversity within the viral quasispecies. This correlation could explain why a group of LTNP-EC patients developed a broad neutralizing response despite having undetectable levels of viremia.

No MeSH data available.


Related in: MedlinePlus

Phylogenetic tree in the C2-V5 env region for LTNP patients and HIV-1 reference viruses.Sequences in the C2-V5 region in env gene, obtained by limiting dilution, from the three DI patients, the matched single infected individuals LTNP 17–1 (filled dark blue triangle),17–2 (empty dark blue triangle), and 17–3 (light blue triangle) GeneBank accession number KC 595042–595055, LTNP 2–1 (purple triangle), 2–3 (pink triangle) GeneBank accession number KC595056-595080, LTNP 20–1 (green triangle) GeneBank accession numbers (KC595081-2 and KC 595237), LTNP 21–2 (filled grey triangle), 21–4 (empty grey triangle) and 21–5 (grey diamond) and 21–6 (grey square) (GeneBank accession numbers KC 59546–48, and KT203901-13) and LTNP 3–2 (yellow triangle) (GeneBank accession numbers KT203872-80) and sequences from reference viruses, LTNP and chronic progressor Spanish patients were included in the analysis. Overall, 180 sequences were subjected to phylogenetic analysis using the Maximum Composite Likelihood method in the MEGA5 program. Two sequences from subtype B viruses (89SP061 and HXB2 with GeneBank accession numbers AJ006287 and K03455, respectively) were included (black star). A subtype D sequence (D.CD.83.ELI, GeneBank accession number K03454I) indicated by grey star was also included as out-group. Sequences were obtained from the LANL database (http://www.hiv.lanl.gov). Only bootstrap values above 80% are marked. Double infected patients are included in a box and with the following symbols MDM-3 (green circle), MDM-4 (empty green circle), MDM 5 (light green circle),MDM 6 (green square) GeneBank accession numbers KC 594991–595006, LTNP-5–1 (yellow circle), 5–2 (empty yellow square), 5–3 (filled yellow circle), 5–4 (empty yellow diamond), 5–6 (yellow diamond), 5–7 (empty light yellow diamond), 5–9 (yellow square) GeneBank accession numbers K595120-145 and KT203881-90 LTNP-15-1 (red circle) and 15–3 (empty red circle) (GeneBank accession numbers KT203891-900). Bar corresponds to genetic distance.
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pone.0134054.g001: Phylogenetic tree in the C2-V5 env region for LTNP patients and HIV-1 reference viruses.Sequences in the C2-V5 region in env gene, obtained by limiting dilution, from the three DI patients, the matched single infected individuals LTNP 17–1 (filled dark blue triangle),17–2 (empty dark blue triangle), and 17–3 (light blue triangle) GeneBank accession number KC 595042–595055, LTNP 2–1 (purple triangle), 2–3 (pink triangle) GeneBank accession number KC595056-595080, LTNP 20–1 (green triangle) GeneBank accession numbers (KC595081-2 and KC 595237), LTNP 21–2 (filled grey triangle), 21–4 (empty grey triangle) and 21–5 (grey diamond) and 21–6 (grey square) (GeneBank accession numbers KC 59546–48, and KT203901-13) and LTNP 3–2 (yellow triangle) (GeneBank accession numbers KT203872-80) and sequences from reference viruses, LTNP and chronic progressor Spanish patients were included in the analysis. Overall, 180 sequences were subjected to phylogenetic analysis using the Maximum Composite Likelihood method in the MEGA5 program. Two sequences from subtype B viruses (89SP061 and HXB2 with GeneBank accession numbers AJ006287 and K03455, respectively) were included (black star). A subtype D sequence (D.CD.83.ELI, GeneBank accession number K03454I) indicated by grey star was also included as out-group. Sequences were obtained from the LANL database (http://www.hiv.lanl.gov). Only bootstrap values above 80% are marked. Double infected patients are included in a box and with the following symbols MDM-3 (green circle), MDM-4 (empty green circle), MDM 5 (light green circle),MDM 6 (green square) GeneBank accession numbers KC 594991–595006, LTNP-5–1 (yellow circle), 5–2 (empty yellow square), 5–3 (filled yellow circle), 5–4 (empty yellow diamond), 5–6 (yellow diamond), 5–7 (empty light yellow diamond), 5–9 (yellow square) GeneBank accession numbers K595120-145 and KT203881-90 LTNP-15-1 (red circle) and 15–3 (empty red circle) (GeneBank accession numbers KT203891-900). Bar corresponds to genetic distance.

Mentions: Sequences in the C2-V5 region in the env gene from LTNP-15 were obtained by limiting dilution amplification and subjected to phylogenetic analysis together with sequences from DI patients (MDM, LTNP-5), LTNP-mono-infected patients and reference viruses [18,19]. For all patients, at least two samples belonging to different time points were included in the phylogenetic analysis. Nucleotide sequences obtained from LTNP-15 clustered in two groups (15a and 15b) with bootstrap values of 75 and 82 respectively (Fig 1). This analysis confirmed that patient LTNP-15 was dually infected according to the previously reported criteria [19].


HIV-1 Dual Infected LTNP-EC Patients Developed an Unexpected Antibody Cross-Neutralizing Activity.

Pernas M, Sanchez-Merino V, Casado C, Merino-Mansilla A, Olivares I, Yuste E, Lopez-Galindez C - PLoS ONE (2015)

Phylogenetic tree in the C2-V5 env region for LTNP patients and HIV-1 reference viruses.Sequences in the C2-V5 region in env gene, obtained by limiting dilution, from the three DI patients, the matched single infected individuals LTNP 17–1 (filled dark blue triangle),17–2 (empty dark blue triangle), and 17–3 (light blue triangle) GeneBank accession number KC 595042–595055, LTNP 2–1 (purple triangle), 2–3 (pink triangle) GeneBank accession number KC595056-595080, LTNP 20–1 (green triangle) GeneBank accession numbers (KC595081-2 and KC 595237), LTNP 21–2 (filled grey triangle), 21–4 (empty grey triangle) and 21–5 (grey diamond) and 21–6 (grey square) (GeneBank accession numbers KC 59546–48, and KT203901-13) and LTNP 3–2 (yellow triangle) (GeneBank accession numbers KT203872-80) and sequences from reference viruses, LTNP and chronic progressor Spanish patients were included in the analysis. Overall, 180 sequences were subjected to phylogenetic analysis using the Maximum Composite Likelihood method in the MEGA5 program. Two sequences from subtype B viruses (89SP061 and HXB2 with GeneBank accession numbers AJ006287 and K03455, respectively) were included (black star). A subtype D sequence (D.CD.83.ELI, GeneBank accession number K03454I) indicated by grey star was also included as out-group. Sequences were obtained from the LANL database (http://www.hiv.lanl.gov). Only bootstrap values above 80% are marked. Double infected patients are included in a box and with the following symbols MDM-3 (green circle), MDM-4 (empty green circle), MDM 5 (light green circle),MDM 6 (green square) GeneBank accession numbers KC 594991–595006, LTNP-5–1 (yellow circle), 5–2 (empty yellow square), 5–3 (filled yellow circle), 5–4 (empty yellow diamond), 5–6 (yellow diamond), 5–7 (empty light yellow diamond), 5–9 (yellow square) GeneBank accession numbers K595120-145 and KT203881-90 LTNP-15-1 (red circle) and 15–3 (empty red circle) (GeneBank accession numbers KT203891-900). Bar corresponds to genetic distance.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4530867&req=5

pone.0134054.g001: Phylogenetic tree in the C2-V5 env region for LTNP patients and HIV-1 reference viruses.Sequences in the C2-V5 region in env gene, obtained by limiting dilution, from the three DI patients, the matched single infected individuals LTNP 17–1 (filled dark blue triangle),17–2 (empty dark blue triangle), and 17–3 (light blue triangle) GeneBank accession number KC 595042–595055, LTNP 2–1 (purple triangle), 2–3 (pink triangle) GeneBank accession number KC595056-595080, LTNP 20–1 (green triangle) GeneBank accession numbers (KC595081-2 and KC 595237), LTNP 21–2 (filled grey triangle), 21–4 (empty grey triangle) and 21–5 (grey diamond) and 21–6 (grey square) (GeneBank accession numbers KC 59546–48, and KT203901-13) and LTNP 3–2 (yellow triangle) (GeneBank accession numbers KT203872-80) and sequences from reference viruses, LTNP and chronic progressor Spanish patients were included in the analysis. Overall, 180 sequences were subjected to phylogenetic analysis using the Maximum Composite Likelihood method in the MEGA5 program. Two sequences from subtype B viruses (89SP061 and HXB2 with GeneBank accession numbers AJ006287 and K03455, respectively) were included (black star). A subtype D sequence (D.CD.83.ELI, GeneBank accession number K03454I) indicated by grey star was also included as out-group. Sequences were obtained from the LANL database (http://www.hiv.lanl.gov). Only bootstrap values above 80% are marked. Double infected patients are included in a box and with the following symbols MDM-3 (green circle), MDM-4 (empty green circle), MDM 5 (light green circle),MDM 6 (green square) GeneBank accession numbers KC 594991–595006, LTNP-5–1 (yellow circle), 5–2 (empty yellow square), 5–3 (filled yellow circle), 5–4 (empty yellow diamond), 5–6 (yellow diamond), 5–7 (empty light yellow diamond), 5–9 (yellow square) GeneBank accession numbers K595120-145 and KT203881-90 LTNP-15-1 (red circle) and 15–3 (empty red circle) (GeneBank accession numbers KT203891-900). Bar corresponds to genetic distance.
Mentions: Sequences in the C2-V5 region in the env gene from LTNP-15 were obtained by limiting dilution amplification and subjected to phylogenetic analysis together with sequences from DI patients (MDM, LTNP-5), LTNP-mono-infected patients and reference viruses [18,19]. For all patients, at least two samples belonging to different time points were included in the phylogenetic analysis. Nucleotide sequences obtained from LTNP-15 clustered in two groups (15a and 15b) with bootstrap values of 75 and 82 respectively (Fig 1). This analysis confirmed that patient LTNP-15 was dually infected according to the previously reported criteria [19].

Bottom Line: Our results showed an improved neutralization breadth in DI LTNP-EC patients when compared with matched LTNP single-infected patients.We found a positive correlation between neutralization breadth and diversity within the viral quasispecies.This correlation could explain why a group of LTNP-EC patients developed a broad neutralizing response despite having undetectable levels of viremia.

View Article: PubMed Central - PubMed

Affiliation: Centro Nacional de Microbiología (CNM), Instituto de Salud Carlos III, Majadahonda, Madrid 28220, Spain.

ABSTRACT
This study evaluated the neutralization breadth in dually infected (DI) HIV-1 long-term non-progressor elite controller patients (LTNP-EC) using a representative minipanel of 6 viruses from 5 different subtypes. Our results showed an improved neutralization breadth in DI LTNP-EC patients when compared with matched LTNP single-infected patients. The role of viral diversity in neutralization was estimated with the Shannon Entropy and the p-distance in viral quasispecies. We found a positive correlation between neutralization breadth and diversity within the viral quasispecies. This correlation could explain why a group of LTNP-EC patients developed a broad neutralizing response despite having undetectable levels of viremia.

No MeSH data available.


Related in: MedlinePlus