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Title: Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection

Abstract

Recombination in HIV-1 is well documented, but its importance in the low-diversity setting of within-host diversification is less understood. Here we develop a novel computational tool (RAPR (Recombination Analysis PRogram)) to enable a detailed view of in vivo viral recombination during early infection, and we apply it to near-full-length HIV-1 genome sequences from longitudinal samples. Recombinant genomes rapidly replace transmitted/founder (T/F) lineages, with a median half-time of 27 days, increasing the genetic complexity of the viral population. We identify recombination hot and cold spots that differ from those observed in inter-subtype recombinants. Furthermore, RAPR analysis of longitudinal samples from an individual with well-characterized neutralizing antibody responses shows that recombination helps carry forward resistance-conferring mutations in the diversifying quasispecies. These findings provide insight into molecular mechanisms by which viral recombination contributes to HIV-1 persistence and immunopathogenesis and have implications for studies of HIV transmission and evolution in vivo.

Authors:
 [1]; ORCiD logo [2];  [3];  [4];  [5];  [2];  [6];  [4]; ORCiD logo [2]; ORCiD logo [2];  [7];  [4];  [6];  [6];  [8];  [9];  [10];  [11];  [4];  [10] more »;  [6];  [6];  [12];  [4]; ORCiD logo [2]; ORCiD logo [2]; ORCiD logo [7] « less
  1. Duke Univ. Medical Center, Durham, NC (United States); Walter Reed Army Institute of Research, Silver Spring, MD (United States)
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  3. Univ. of Tennessee, Knoxville, TN (United States)
  4. Duke Univ. Medical Center, Durham, NC (United States)
  5. Univ. of Arizona, Tucson, AZ (United States)
  6. Univ. of Pennsylvania, Philadelphia, PA (United States)
  7. Duke Univ. Medical Center, Durham, NC (United States); Jilin Univ. (China)
  8. Univ. of Alabama, Birmingham, AL (United States); MRC/UVRI and LSHTM Uganda Research Unit, Entebbe (Uganda)
  9. Univ. of Alabama, Birmingham, AL (United States)
  10. Univ. of North Carolina, Chapel Hill, NC (United States)
  11. Frederick National Laboratory for Cancer Research, Frederick, MD (United States)
  12. Univ. of Oxford (United Kingdom)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE Laboratory Directed Research and Development (LDRD) Program
OSTI Identifier:
1593118
Report Number(s):
LA-UR-19-30217
Journal ID: ISSN 2041-1723
Grant/Contract Number:  
89233218CNA000001; R01AI087520; AI100645; AAI 12007-0000-01000; HHSN261200800001E
Resource Type:
Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Biological Science

Citation Formats

Song, Hongshuo, Giorgi, Elena Edi, Ganusov, Vitaly V., Cai, Fangping, Athreya, Gayathri, Yoon, Hyejin, Carja, Oana, Hora, Bhavna, Hraber, Peter Thomas, Romero-Severson, Ethan, Jiang, Chunlai, Li, Xiaojun, Wang, Shuyi, Li, Hui, Salazar-Gonzalez, Jesus F., Salazar, Maria G., Goonetilleke, Nilu, Keele, Brandon F., Montefiori, David C., Cohen, Myron S., Shaw, George M., Hahn, Beatrice H., McMichael, Andrew J., Haynes, Barton F., Korber, Bette Tina Marie, Bhattacharya, Tanmoy, and Gao, Feng. Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection. United States: N. p., 2018. Web. doi:10.1038/s41467-018-04217-5.
Song, Hongshuo, Giorgi, Elena Edi, Ganusov, Vitaly V., Cai, Fangping, Athreya, Gayathri, Yoon, Hyejin, Carja, Oana, Hora, Bhavna, Hraber, Peter Thomas, Romero-Severson, Ethan, Jiang, Chunlai, Li, Xiaojun, Wang, Shuyi, Li, Hui, Salazar-Gonzalez, Jesus F., Salazar, Maria G., Goonetilleke, Nilu, Keele, Brandon F., Montefiori, David C., Cohen, Myron S., Shaw, George M., Hahn, Beatrice H., McMichael, Andrew J., Haynes, Barton F., Korber, Bette Tina Marie, Bhattacharya, Tanmoy, & Gao, Feng. Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection. United States. doi:10.1038/s41467-018-04217-5.
Song, Hongshuo, Giorgi, Elena Edi, Ganusov, Vitaly V., Cai, Fangping, Athreya, Gayathri, Yoon, Hyejin, Carja, Oana, Hora, Bhavna, Hraber, Peter Thomas, Romero-Severson, Ethan, Jiang, Chunlai, Li, Xiaojun, Wang, Shuyi, Li, Hui, Salazar-Gonzalez, Jesus F., Salazar, Maria G., Goonetilleke, Nilu, Keele, Brandon F., Montefiori, David C., Cohen, Myron S., Shaw, George M., Hahn, Beatrice H., McMichael, Andrew J., Haynes, Barton F., Korber, Bette Tina Marie, Bhattacharya, Tanmoy, and Gao, Feng. Tue . "Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection". United States. doi:10.1038/s41467-018-04217-5. https://www.osti.gov/servlets/purl/1593118.
@article{osti_1593118,
title = {Tracking HIV-1 recombination to resolve its contribution to HIV-1 evolution in natural infection},
author = {Song, Hongshuo and Giorgi, Elena Edi and Ganusov, Vitaly V. and Cai, Fangping and Athreya, Gayathri and Yoon, Hyejin and Carja, Oana and Hora, Bhavna and Hraber, Peter Thomas and Romero-Severson, Ethan and Jiang, Chunlai and Li, Xiaojun and Wang, Shuyi and Li, Hui and Salazar-Gonzalez, Jesus F. and Salazar, Maria G. and Goonetilleke, Nilu and Keele, Brandon F. and Montefiori, David C. and Cohen, Myron S. and Shaw, George M. and Hahn, Beatrice H. and McMichael, Andrew J. and Haynes, Barton F. and Korber, Bette Tina Marie and Bhattacharya, Tanmoy and Gao, Feng},
abstractNote = {Recombination in HIV-1 is well documented, but its importance in the low-diversity setting of within-host diversification is less understood. Here we develop a novel computational tool (RAPR (Recombination Analysis PRogram)) to enable a detailed view of in vivo viral recombination during early infection, and we apply it to near-full-length HIV-1 genome sequences from longitudinal samples. Recombinant genomes rapidly replace transmitted/founder (T/F) lineages, with a median half-time of 27 days, increasing the genetic complexity of the viral population. We identify recombination hot and cold spots that differ from those observed in inter-subtype recombinants. Furthermore, RAPR analysis of longitudinal samples from an individual with well-characterized neutralizing antibody responses shows that recombination helps carry forward resistance-conferring mutations in the diversifying quasispecies. These findings provide insight into molecular mechanisms by which viral recombination contributes to HIV-1 persistence and immunopathogenesis and have implications for studies of HIV transmission and evolution in vivo.},
doi = {10.1038/s41467-018-04217-5},
journal = {Nature Communications},
number = 1,
volume = 9,
place = {United States},
year = {2018},
month = {5}
}

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