Increased Frequency of Inter-Subtype HIV-1 Recombinants Identified by Near Full-Length Virus Sequencing in Rwandan Acute Transmission Cohorts
Most studies of HIV-1 transmission have focused on subtypes B and C. In this study, we determined the genomic sequences of the transmitted founder (TF) viruses from acutely infected individuals enrolled between 2005 and 2011 into IAVI protocol C in Rwanda and have compared these isolates to viruses...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2021.734929/full |
| _version_ | 1818559190897000448 |
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| author | Gisele Umviligihozo Erick Muok Emmanuel Nyirimihigo Gisa Rui Xu Dario Dilernia Kimberley Herard Heeyah Song Qianhong Qin Jean Bizimana Paul Farmer Jonathan Hare Jill Gilmour Susan Allen Etienne Karita Eric Hunter Eric Hunter Ling Yue |
| author_facet | Gisele Umviligihozo Erick Muok Emmanuel Nyirimihigo Gisa Rui Xu Dario Dilernia Kimberley Herard Heeyah Song Qianhong Qin Jean Bizimana Paul Farmer Jonathan Hare Jill Gilmour Susan Allen Etienne Karita Eric Hunter Eric Hunter Ling Yue |
| author_sort | Gisele Umviligihozo |
| collection | DOAJ |
| description | Most studies of HIV-1 transmission have focused on subtypes B and C. In this study, we determined the genomic sequences of the transmitted founder (TF) viruses from acutely infected individuals enrolled between 2005 and 2011 into IAVI protocol C in Rwanda and have compared these isolates to viruses from more recent (2016–2019) acute/early infections in three at risk populations – MSM, high risk women (HRW), and discordant couples (DC). For the Protocol C samples, we utilized near full-length single genome (NFLG) amplification to generate 288 HIV-1 amplicons from 26 acutely infected seroconverters (SC), while for the 21 recent seroconverter samples (13 from HRW, two from DC, and six from MSM), we PCR amplified overlapping half-genomes. Using PacBio SMRT technology combined with the MDPseq workflow, we performed multiplex sequencing to obtain high accuracy sequences for each amplicon. Phylogenetic analyses indicated that the majority of recent transmitted viruses from DC and HRW clustered within those of the earlier Protocol C cohort. However, five of six sequences from the MSM cohort branched together and were greater than 97% identical. Recombination analyses revealed a high frequency (6/26; 23%) of unique inter-subtype recombination in Protocol C with 19% AC and 4% CD recombinant viruses, which contrasted with only 6.5% of recombinants defined by sequencing of the pol gene previously. The frequency of recombinants was significantly higher (12/21; 57%) in the more recent isolates, although, the five related viruses from the MSM cohort had identical recombination break points. While major drug resistance mutations were absent from Protocol C viruses, 4/21 of recent isolates exhibited transmitted nevirapine resistance. These results demonstrate the ongoing evolution and increased prevalence of recombinant and drug resistant transmitted viruses in Rwanda and highlight the importance of defining NFLG sequences to fully understand the nature of TF viruses and in particular the prevalence of unique recombinant forms (URFs) in transmission cohorts. |
| first_indexed | 2024-12-14T00:22:11Z |
| format | Article |
| id | doaj.art-7da2e3b82b044ac6a40fc81526c004cc |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-14T00:22:11Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-7da2e3b82b044ac6a40fc81526c004cc2022-12-21T23:25:10ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2021-10-011210.3389/fmicb.2021.734929734929Increased Frequency of Inter-Subtype HIV-1 Recombinants Identified by Near Full-Length Virus Sequencing in Rwandan Acute Transmission CohortsGisele Umviligihozo0Erick Muok1Emmanuel Nyirimihigo Gisa2Rui Xu3Dario Dilernia4Kimberley Herard5Heeyah Song6Qianhong Qin7Jean Bizimana8Paul Farmer9Jonathan Hare10Jill Gilmour11Susan Allen12Etienne Karita13Eric Hunter14Eric Hunter15Ling Yue16Centre for Family Health Research, Kigali, RwandaCentre for Family Health Research, Kigali, RwandaCentre for Family Health Research, Kigali, RwandaEmory Vaccine Center at Yerkes National Primate Research Center, Atlanta, GA, United StatesEmory Vaccine Center at Yerkes National Primate Research Center, Atlanta, GA, United StatesEmory Vaccine Center at Yerkes National Primate Research Center, Atlanta, GA, United StatesEmory Vaccine Center at Yerkes National Primate Research Center, Atlanta, GA, United StatesEmory Vaccine Center at Yerkes National Primate Research Center, Atlanta, GA, United StatesCentre for Family Health Research, Kigali, RwandaEmory Vaccine Center at Yerkes National Primate Research Center, Atlanta, GA, United StatesIAVI, New York, NY, United StatesFaculty of Medicine, Imperial College London, London, United KingdomDepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United StatesCentre for Family Health Research, Kigali, RwandaEmory Vaccine Center at Yerkes National Primate Research Center, Atlanta, GA, United StatesDepartment of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, United StatesEmory Vaccine Center at Yerkes National Primate Research Center, Atlanta, GA, United StatesMost studies of HIV-1 transmission have focused on subtypes B and C. In this study, we determined the genomic sequences of the transmitted founder (TF) viruses from acutely infected individuals enrolled between 2005 and 2011 into IAVI protocol C in Rwanda and have compared these isolates to viruses from more recent (2016–2019) acute/early infections in three at risk populations – MSM, high risk women (HRW), and discordant couples (DC). For the Protocol C samples, we utilized near full-length single genome (NFLG) amplification to generate 288 HIV-1 amplicons from 26 acutely infected seroconverters (SC), while for the 21 recent seroconverter samples (13 from HRW, two from DC, and six from MSM), we PCR amplified overlapping half-genomes. Using PacBio SMRT technology combined with the MDPseq workflow, we performed multiplex sequencing to obtain high accuracy sequences for each amplicon. Phylogenetic analyses indicated that the majority of recent transmitted viruses from DC and HRW clustered within those of the earlier Protocol C cohort. However, five of six sequences from the MSM cohort branched together and were greater than 97% identical. Recombination analyses revealed a high frequency (6/26; 23%) of unique inter-subtype recombination in Protocol C with 19% AC and 4% CD recombinant viruses, which contrasted with only 6.5% of recombinants defined by sequencing of the pol gene previously. The frequency of recombinants was significantly higher (12/21; 57%) in the more recent isolates, although, the five related viruses from the MSM cohort had identical recombination break points. While major drug resistance mutations were absent from Protocol C viruses, 4/21 of recent isolates exhibited transmitted nevirapine resistance. These results demonstrate the ongoing evolution and increased prevalence of recombinant and drug resistant transmitted viruses in Rwanda and highlight the importance of defining NFLG sequences to fully understand the nature of TF viruses and in particular the prevalence of unique recombinant forms (URFs) in transmission cohorts.https://www.frontiersin.org/articles/10.3389/fmicb.2021.734929/fullHIV-1 transmissiongenetic bottleneckHIV subtypeinter-subtype recombinationantiretroviral drug resistance mutationsnear full-length genome sequencing |
| spellingShingle | Gisele Umviligihozo Erick Muok Emmanuel Nyirimihigo Gisa Rui Xu Dario Dilernia Kimberley Herard Heeyah Song Qianhong Qin Jean Bizimana Paul Farmer Jonathan Hare Jill Gilmour Susan Allen Etienne Karita Eric Hunter Eric Hunter Ling Yue Increased Frequency of Inter-Subtype HIV-1 Recombinants Identified by Near Full-Length Virus Sequencing in Rwandan Acute Transmission Cohorts Frontiers in Microbiology HIV-1 transmission genetic bottleneck HIV subtype inter-subtype recombination antiretroviral drug resistance mutations near full-length genome sequencing |
| title | Increased Frequency of Inter-Subtype HIV-1 Recombinants Identified by Near Full-Length Virus Sequencing in Rwandan Acute Transmission Cohorts |
| title_full | Increased Frequency of Inter-Subtype HIV-1 Recombinants Identified by Near Full-Length Virus Sequencing in Rwandan Acute Transmission Cohorts |
| title_fullStr | Increased Frequency of Inter-Subtype HIV-1 Recombinants Identified by Near Full-Length Virus Sequencing in Rwandan Acute Transmission Cohorts |
| title_full_unstemmed | Increased Frequency of Inter-Subtype HIV-1 Recombinants Identified by Near Full-Length Virus Sequencing in Rwandan Acute Transmission Cohorts |
| title_short | Increased Frequency of Inter-Subtype HIV-1 Recombinants Identified by Near Full-Length Virus Sequencing in Rwandan Acute Transmission Cohorts |
| title_sort | increased frequency of inter subtype hiv 1 recombinants identified by near full length virus sequencing in rwandan acute transmission cohorts |
| topic | HIV-1 transmission genetic bottleneck HIV subtype inter-subtype recombination antiretroviral drug resistance mutations near full-length genome sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2021.734929/full |
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