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203,234 studies31 sourcesUpdated 39 min ago
Peer-reviewedCC BYNature Communications

Long-read deep sequencing reveals high rates of multilineage transmission and rapid viral population changes in acute HIV infection

  • James I. Mullins1,2
  • Wenjie Deng3,4,2
  • Elena E. Giorgi4,5
  • Craig A. Magaret4,5
  • Morgane Rolland6,7,8
  • Tanmoy Bhattacharya A9,10,11
  • Dylan H. Westfall3,4,2
  • Anna Yssel12,13,14
  • Roger E. Bumgarner3,2
  • Ben Murrell15,16
  • Thumbi Ndung’u17,18,19,20,21
  • Merlin Lee Robb6,22
23 more authors
  • Raabya Rossenkhan4,5
  • Paul T. Edlefsen4,5
  • Krista L. Dong20,23
  • Lennie Chen3,2
  • Asanda Gwashu-Nyangiri12,14
  • Hong Zhao3,24,2
  • Ruwayhida Thebus12,14
  • Nonkululeko Ndabambi12,25
  • Bruna Galvão12,26
  • Fredrick Sawe27,28,14
  • Sorachai Nitayaphan29,14
  • Talita York12,14
  • David Matten12,2
  • Hugh Murrell12,5
  • Alec P. Pankow30,3,5
  • Michal Juraska4,5
  • James Ludwig4,31
  • John Hural4,5
  • Myron S. Cohen32,5
  • Lawrence Corey4,5
  • M. Juliana McElrath4,14
  • Peter B. Gilbert4
  • Carolyn E. Williamson12,33
33 affiliations
  1. 1Department of Microbiology, University of Washington, Seattle, WA, USA. [email protected]
  2. 2University of Washington
  3. 3Department of Microbiology, University of Washington, Seattle, WA, USA
  4. 4Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA
  5. 5Fred Hutchinson Cancer Center
  6. 6Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc, Bethesda, MD, USA
  7. 7U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
  8. 8Henry M. Jackson Foundation for the Advancement of Military Medicine,
  9. 9Santa Fe Institute, Santa Fe, NM, USA
  10. 10Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM, USA
  11. 11Los Alamos National Laboratory
  12. 12Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, University of Cape Town, Cape Town, South Africa
  13. 13Sand Technologies, Cape Town, South Africa
  14. 14University of Cape Town
  15. 15Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
  16. 16Karolinska Institutet
  17. 17African Health Research Institute, University of KwaZulu Natal, Durban, South Africa
  18. 18Division of Infection and Immunity, University College London, London, UK
  19. 19HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa
  20. 20Ragon Institute of Mass General Brigham, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA
  21. 21University of KwaZulu Natal
  22. 22Henry M. Jackson Foundation for the Advancement of Military Medicine
  23. 23Ragon Institute of Mass General Brigham
  24. 24Department of Obstetrics and Gynecology, University of Washington, Seattle, WA, USA
  25. 25Kenya Medical Research Institute
  26. 26Armed Forces Research Institute of Medical Sciences
  27. 27Henry M. Jackson Foundation Medical Research International, Nairobi, Kenya
  28. 28Kenya Medical Research Institute, Walter Reed Army Institute of Research-Africa, Nairobi, Kenya
  29. 29Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand
  30. 30Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  31. 31University of North Carolina
  32. 32University of North Carolina, Chapel Hill, NC, USA
  33. 33National Health Laboratory Services, Johannesburg, South Africa
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Abstract

Understanding the selective forces acting upon HIV early in infection is crucial to design prevention strategies. By leveraging deep sequencing and the short diagnostic intervals of the FRESH and RV217 cohorts between the last-negative and first-positive RNA tests (median 4 days), we captured a precise and early snapshot of acute HIV infection. The frequency of multiple transmitted viruses of 37% in these as well as placebo recipients from the AMP trials (NCT02716675 and NCT02568215) was higher than previously published, with the true frequency likely to be higher. The relative abundance of lineages fluctuated substantially over time in two-thirds of the multilineage infections, generating uncertainty in identifying the specific viruses that were transmitted and founding the infection. At the population level, viral populations exhibited limited diversity and selection on the Gag and Env proteins at the earliest times examined, with sites inferred to be undergoing negative selection most evident. These data may help explain vaccination failures and provide new targets for prevention.

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Cite

BibTeXRIS
BibTeX
@article{mullins2026longread,
  title = {{Long-read deep sequencing reveals high rates of multilineage transmission and rapid viral population changes in acute HIV infection}},
  author = {James I. Mullins and Wenjie Deng and Elena E. Giorgi and Craig A. Magaret and Morgane Rolland and Tanmoy Bhattacharya A and Dylan H. Westfall and Anna Yssel and Roger E. Bumgarner and Ben Murrell and Thumbi Ndung’u and Merlin Lee Robb and Raabya Rossenkhan and Paul T. Edlefsen and Krista L. Dong and Lennie Chen and Asanda Gwashu-Nyangiri and Hong Zhao and Ruwayhida Thebus and Nonkululeko Ndabambi and Bruna Galvão and Fredrick Sawe and Sorachai Nitayaphan and Talita York and David Matten and Hugh Murrell and Alec P. Pankow and Michal Juraska and James Ludwig and John Hural and Myron S. Cohen and Lawrence Corey and M. Juliana McElrath and Peter B. Gilbert and Carolyn E. Williamson},
  journal = {Nature Communications},
  year = {2026},
  month = may,
  doi = {10.1038/s41467-026-73496-0},
  url = {https://doi.org/10.1038/s41467-026-73496-0},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Long-read deep sequencing reveals high rates of multilineage transmission and rapid viral population changes in acute HIV infection
AU  - James I. Mullins
AU  - Wenjie Deng
AU  - Elena E. Giorgi
AU  - Craig A. Magaret
AU  - Morgane Rolland
AU  - Tanmoy Bhattacharya A
AU  - Dylan H. Westfall
AU  - Anna Yssel
AU  - Roger E. Bumgarner
AU  - Ben Murrell
AU  - Thumbi Ndung’u
AU  - Merlin Lee Robb
AU  - Raabya Rossenkhan
AU  - Paul T. Edlefsen
AU  - Krista L. Dong
AU  - Lennie Chen
AU  - Asanda Gwashu-Nyangiri
AU  - Hong Zhao
AU  - Ruwayhida Thebus
AU  - Nonkululeko Ndabambi
AU  - Bruna Galvão
AU  - Fredrick Sawe
AU  - Sorachai Nitayaphan
AU  - Talita York
AU  - David Matten
AU  - Hugh Murrell
AU  - Alec P. Pankow
AU  - Michal Juraska
AU  - James Ludwig
AU  - John Hural
AU  - Myron S. Cohen
AU  - Lawrence Corey
AU  - M. Juliana McElrath
AU  - Peter B. Gilbert
AU  - Carolyn E. Williamson
PY  - 2026
DA  - 2026/05/25
JO  - Nature Communications
DO  - 10.1038/s41467-026-73496-0
UR  - https://doi.org/10.1038/s41467-026-73496-0
AB  - Understanding the selective forces acting upon HIV early in infection is crucial to design prevention strategies. By leveraging deep sequencing and the short diagnostic intervals of the FRESH and RV217 cohorts between the last-negative and first-positive RNA tests (median 4 days), we captured a precise and early snapshot of acute HIV infection. The frequency of multiple transmitted viruses of 37% in these as well as placebo recipients from the AMP trials (NCT02716675 and NCT02568215) was higher than previously published, with the true frequency likely to be higher. The relative abundance of lineages fluctuated substantially over time in two-thirds of the multilineage infections, generating uncertainty in identifying the specific viruses that were transmitted and founding the infection. At the population level, viral populations exhibited limited diversity and selection on the Gag and Env proteins at the earliest times examined, with sites inferred to be undergoing negative selection most evident. These data may help explain vaccination failures and provide new targets for prevention.
SN  - 2041-1723
ER  -