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The Number and Complexity of Pure and Recombinant HIV-1 Strains Observed within Incident Infections during the HIV and Malaria Cohort Study Conducted in Kericho, Kenya, from 2003 to 2006.

Billings E, Sanders-Buell E, Bose M, Bradfield A, Lei E, Kijak GH, Arroyo MA, Kibaya RM, Scott PT, Wasunna MK, Sawe FK, Shaffer DN, Birx DL, McCutchan FE, Michael NL, Robb ML, Kim JH, Tovanabutra S - PLoS ONE (2015)

Bottom Line: This diversity and the resulting genetic distance between the observed strains will need to be addressed when vaccine immunogens are chosen.In consideration of current vaccine development efforts, the strains from these three studies were compared to five candidate vaccines (each of which are viral vectored, carrying inserts corresponding to parts of gag, pol, and envelope), which have been developed for possible use in sub-Saharan Africa.The sequence comparison between the observed strains and the candidate vaccines indicates that in the presence of diverse recombinants, a bivalent vaccine is more likely to provide T-cell epitope coverage than monovalent vaccines even when the inserts of the bivalent vaccine are not subtype-matched to the local epidemic.

View Article: PubMed Central - PubMed

Affiliation: United States Military HIV Research Program/Henry M. Jackson Foundation, Rockville, Maryland, United States of America.

ABSTRACT
Characterization of HIV-1 subtype diversity in regions where vaccine trials are conducted is critical for vaccine development and testing. This study describes the molecular epidemiology of HIV-1 within a tea-plantation community cohort in Kericho, Kenya. Sixty-three incident infections were ascertained in the HIV and Malaria Cohort Study conducted in Kericho from 2003 to 2006. HIV-1 strains from 58 of those individuals were full genome characterized and compared to two previous Kenyan studies describing 41 prevalent infections from a blood bank survey (1999-2000) and 21 infections from a higher-risk cohort containing a mix of incident and prevalent infections (2006). Among the 58 strains from the community cohort, 43.1% were pure subtypes (36.2% A1, 5.2% C, and 1.7% G) and 56.9% were inter-subtype recombinants (29.3% A1D, 8.6% A1CD, 6.9% A1A2D, 5.2% A1C, 3.4% A1A2CD, and 3.4% A2D). This diversity and the resulting genetic distance between the observed strains will need to be addressed when vaccine immunogens are chosen. In consideration of current vaccine development efforts, the strains from these three studies were compared to five candidate vaccines (each of which are viral vectored, carrying inserts corresponding to parts of gag, pol, and envelope), which have been developed for possible use in sub-Saharan Africa. The sequence comparison between the observed strains and the candidate vaccines indicates that in the presence of diverse recombinants, a bivalent vaccine is more likely to provide T-cell epitope coverage than monovalent vaccines even when the inserts of the bivalent vaccine are not subtype-matched to the local epidemic.

No MeSH data available.


Related in: MedlinePlus

Genome structures of 33 HIV-1 recombinant strains identified during this community cohort incident infection study.(a) The incident recombinant genomes are depicted in relation to the HXB2 reference strain. Each colored region represents the predicted parent subtype based on the results from Recombinant Breakpoint Analysis; subtype A1 is shown in red, A2 in pink, C in yellow, and D in blue. (b) The two A2D strains with similar structures are shown compared to the CRF16_A2D reference breakpoints from hiv.lanl.gov. The A2D strains do appear to be CRF16_A2D infections, but are not directly linked (see text).
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pone.0135124.g004: Genome structures of 33 HIV-1 recombinant strains identified during this community cohort incident infection study.(a) The incident recombinant genomes are depicted in relation to the HXB2 reference strain. Each colored region represents the predicted parent subtype based on the results from Recombinant Breakpoint Analysis; subtype A1 is shown in red, A2 in pink, C in yellow, and D in blue. (b) The two A2D strains with similar structures are shown compared to the CRF16_A2D reference breakpoints from hiv.lanl.gov. The A2D strains do appear to be CRF16_A2D infections, but are not directly linked (see text).

Mentions: A phylogenetic tree of recombinant strains from the current and previous studies (Fig 3) shows an interspersed pattern similar to that seen between the pure subtype strains, with large clusters divided between the parent subtypes A1/A2, C, and D. Within the A1/A2 cluster, two A2D strains (05KE493170V5 and 05KE725124V4) are closely related to the CRF16_A2D variant and reference sequences, collectively forming a distinct sub-cluster. As expected, the two previously mentioned A2D strains have very similar genome structures (Fig 4B); however, those two infections do not appear to have direct epidemiological linkage, as indicated by the full genome pairwise distance of 9.7% (SE 0.3%) between the two strains. For comparison, the full genome pairwise distance between unlinked individuals within this dataset was estimated by separately analyzing the five sequences within the CRF16_A2D sub-cluster, which yielded a median pairwise distance of 10.4% (range: 8.9–11.4%), and the 20 non-linked pure A1 genomes which yielded a median distance of 10.8% (range: 6.7–13.7%). Recombinant Breakpoint Analysis of the 33 recombinant forms observed in this study shows a large amount of diversity. The genome structures (Fig 4A) vary from a simple recombinant with 2 breakpoints to a very complex genome with 22 breakpoints. Other than the two strains that were closely related to CRF16_A2D, the rest of the recombinants were newly identified unique recombinant forms. Further confirmation of the genomic structure of the observed CRF16_A2D strains was obtained by performing additional breakpoint analysis of the entire CRF16 cluster using the SimPlot [37] analytical suite, with care given to include subtype D reference sequences used during the initial identification and analysis [38,39] of CRF16_A2D (S2 Fig).


The Number and Complexity of Pure and Recombinant HIV-1 Strains Observed within Incident Infections during the HIV and Malaria Cohort Study Conducted in Kericho, Kenya, from 2003 to 2006.

Billings E, Sanders-Buell E, Bose M, Bradfield A, Lei E, Kijak GH, Arroyo MA, Kibaya RM, Scott PT, Wasunna MK, Sawe FK, Shaffer DN, Birx DL, McCutchan FE, Michael NL, Robb ML, Kim JH, Tovanabutra S - PLoS ONE (2015)

Genome structures of 33 HIV-1 recombinant strains identified during this community cohort incident infection study.(a) The incident recombinant genomes are depicted in relation to the HXB2 reference strain. Each colored region represents the predicted parent subtype based on the results from Recombinant Breakpoint Analysis; subtype A1 is shown in red, A2 in pink, C in yellow, and D in blue. (b) The two A2D strains with similar structures are shown compared to the CRF16_A2D reference breakpoints from hiv.lanl.gov. The A2D strains do appear to be CRF16_A2D infections, but are not directly linked (see text).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4543584&req=5

pone.0135124.g004: Genome structures of 33 HIV-1 recombinant strains identified during this community cohort incident infection study.(a) The incident recombinant genomes are depicted in relation to the HXB2 reference strain. Each colored region represents the predicted parent subtype based on the results from Recombinant Breakpoint Analysis; subtype A1 is shown in red, A2 in pink, C in yellow, and D in blue. (b) The two A2D strains with similar structures are shown compared to the CRF16_A2D reference breakpoints from hiv.lanl.gov. The A2D strains do appear to be CRF16_A2D infections, but are not directly linked (see text).
Mentions: A phylogenetic tree of recombinant strains from the current and previous studies (Fig 3) shows an interspersed pattern similar to that seen between the pure subtype strains, with large clusters divided between the parent subtypes A1/A2, C, and D. Within the A1/A2 cluster, two A2D strains (05KE493170V5 and 05KE725124V4) are closely related to the CRF16_A2D variant and reference sequences, collectively forming a distinct sub-cluster. As expected, the two previously mentioned A2D strains have very similar genome structures (Fig 4B); however, those two infections do not appear to have direct epidemiological linkage, as indicated by the full genome pairwise distance of 9.7% (SE 0.3%) between the two strains. For comparison, the full genome pairwise distance between unlinked individuals within this dataset was estimated by separately analyzing the five sequences within the CRF16_A2D sub-cluster, which yielded a median pairwise distance of 10.4% (range: 8.9–11.4%), and the 20 non-linked pure A1 genomes which yielded a median distance of 10.8% (range: 6.7–13.7%). Recombinant Breakpoint Analysis of the 33 recombinant forms observed in this study shows a large amount of diversity. The genome structures (Fig 4A) vary from a simple recombinant with 2 breakpoints to a very complex genome with 22 breakpoints. Other than the two strains that were closely related to CRF16_A2D, the rest of the recombinants were newly identified unique recombinant forms. Further confirmation of the genomic structure of the observed CRF16_A2D strains was obtained by performing additional breakpoint analysis of the entire CRF16 cluster using the SimPlot [37] analytical suite, with care given to include subtype D reference sequences used during the initial identification and analysis [38,39] of CRF16_A2D (S2 Fig).

Bottom Line: This diversity and the resulting genetic distance between the observed strains will need to be addressed when vaccine immunogens are chosen.In consideration of current vaccine development efforts, the strains from these three studies were compared to five candidate vaccines (each of which are viral vectored, carrying inserts corresponding to parts of gag, pol, and envelope), which have been developed for possible use in sub-Saharan Africa.The sequence comparison between the observed strains and the candidate vaccines indicates that in the presence of diverse recombinants, a bivalent vaccine is more likely to provide T-cell epitope coverage than monovalent vaccines even when the inserts of the bivalent vaccine are not subtype-matched to the local epidemic.

View Article: PubMed Central - PubMed

Affiliation: United States Military HIV Research Program/Henry M. Jackson Foundation, Rockville, Maryland, United States of America.

ABSTRACT
Characterization of HIV-1 subtype diversity in regions where vaccine trials are conducted is critical for vaccine development and testing. This study describes the molecular epidemiology of HIV-1 within a tea-plantation community cohort in Kericho, Kenya. Sixty-three incident infections were ascertained in the HIV and Malaria Cohort Study conducted in Kericho from 2003 to 2006. HIV-1 strains from 58 of those individuals were full genome characterized and compared to two previous Kenyan studies describing 41 prevalent infections from a blood bank survey (1999-2000) and 21 infections from a higher-risk cohort containing a mix of incident and prevalent infections (2006). Among the 58 strains from the community cohort, 43.1% were pure subtypes (36.2% A1, 5.2% C, and 1.7% G) and 56.9% were inter-subtype recombinants (29.3% A1D, 8.6% A1CD, 6.9% A1A2D, 5.2% A1C, 3.4% A1A2CD, and 3.4% A2D). This diversity and the resulting genetic distance between the observed strains will need to be addressed when vaccine immunogens are chosen. In consideration of current vaccine development efforts, the strains from these three studies were compared to five candidate vaccines (each of which are viral vectored, carrying inserts corresponding to parts of gag, pol, and envelope), which have been developed for possible use in sub-Saharan Africa. The sequence comparison between the observed strains and the candidate vaccines indicates that in the presence of diverse recombinants, a bivalent vaccine is more likely to provide T-cell epitope coverage than monovalent vaccines even when the inserts of the bivalent vaccine are not subtype-matched to the local epidemic.

No MeSH data available.


Related in: MedlinePlus