Higher HIV-1 evolutionary rate is associated with cytotoxic T lymphocyte escape mutations in infants
(2024) In Journal of Virology 98(7).- Abstract
Escape from cytotoxic T lymphocyte (CTL) responses toward HIV-1 Gag and Nef has been associated with reduced control of HIV-1 replication in adults. However, less is known about CTL-driven immune selection in infants as longitudinal studies of infants are limited. Here, 1,210 gag and 1,264 nef sequences longitudinally collected within 15 months after birth from 14 HIV-1 perinatally infected infants and their mothers were analyzed. The number of transmitted founder (T/F) viruses and associations between virus evolution, selection, CTL escape, and disease progression were determined. The analyses indicated that a paraphyletic-monophyletic relationship between the mother-infant sequences was common (80%), and that the HIV-1 infection was... (More)
Escape from cytotoxic T lymphocyte (CTL) responses toward HIV-1 Gag and Nef has been associated with reduced control of HIV-1 replication in adults. However, less is known about CTL-driven immune selection in infants as longitudinal studies of infants are limited. Here, 1,210 gag and 1,264 nef sequences longitudinally collected within 15 months after birth from 14 HIV-1 perinatally infected infants and their mothers were analyzed. The number of transmitted founder (T/F) viruses and associations between virus evolution, selection, CTL escape, and disease progression were determined. The analyses indicated that a paraphyletic-monophyletic relationship between the mother-infant sequences was common (80%), and that the HIV-1 infection was established by a single T/F virus in 10 of the 12 analyzed infants (83%). Furthermore, most HIV-1 CTL escape mutations among infants were transmitted from the mothers and did not revert during the first year of infection. Still, immune-driven selection was observed at approximately 3 months after HIV-1 infection in infants. Moreover, virus populations with CTL escape mutations in gag evolved faster than those without, independently of disease progression rate. These findings expand the current knowledge of HIV-1 transmission, evolution, and CTL escape in infant HIV-1 infection and are relevant for the development of immune-directed interventions in infants.
(Less)
- author
- organization
- publishing date
- 2024-07-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- CTL responses, disease progression, HIV-1, infant, intra-host evolution, vertical transmission
- in
- Journal of Virology
- volume
- 98
- issue
- 7
- publisher
- American Society for Microbiology
- external identifiers
-
- pmid:38814066
- scopus:85199813086
- ISSN
- 0022-538X
- DOI
- 10.1128/jvi.00072-24
- language
- English
- LU publication?
- yes
- id
- c35f533e-f5d5-4bf6-91ff-17acb3dcd10c
- date added to LUP
- 2024-09-23 14:05:44
- date last changed
- 2024-09-24 03:04:57
@article{c35f533e-f5d5-4bf6-91ff-17acb3dcd10c, abstract = {{<p>Escape from cytotoxic T lymphocyte (CTL) responses toward HIV-1 Gag and Nef has been associated with reduced control of HIV-1 replication in adults. However, less is known about CTL-driven immune selection in infants as longitudinal studies of infants are limited. Here, 1,210 gag and 1,264 nef sequences longitudinally collected within 15 months after birth from 14 HIV-1 perinatally infected infants and their mothers were analyzed. The number of transmitted founder (T/F) viruses and associations between virus evolution, selection, CTL escape, and disease progression were determined. The analyses indicated that a paraphyletic-monophyletic relationship between the mother-infant sequences was common (80%), and that the HIV-1 infection was established by a single T/F virus in 10 of the 12 analyzed infants (83%). Furthermore, most HIV-1 CTL escape mutations among infants were transmitted from the mothers and did not revert during the first year of infection. Still, immune-driven selection was observed at approximately 3 months after HIV-1 infection in infants. Moreover, virus populations with CTL escape mutations in gag evolved faster than those without, independently of disease progression rate. These findings expand the current knowledge of HIV-1 transmission, evolution, and CTL escape in infant HIV-1 infection and are relevant for the development of immune-directed interventions in infants.</p>}}, author = {{Nazziwa, Jamirah and Andrews, Sophie M. and Hou, Mimi M. and Bruhn, Christian A.W. and Garcia-Knight, Miguel A. and Slyker, Jennifer and Hill, Sarah and Payne, Barbara Lohman and Moringas, Dorothy and Lemey, Philippe and John-Stewart, Grace and Rowland-Jones, Sarah L. and Esbjörnsson, Joakim}}, issn = {{0022-538X}}, keywords = {{CTL responses; disease progression; HIV-1; infant; intra-host evolution; vertical transmission}}, language = {{eng}}, month = {{07}}, number = {{7}}, publisher = {{American Society for Microbiology}}, series = {{Journal of Virology}}, title = {{Higher HIV-1 evolutionary rate is associated with cytotoxic T lymphocyte escape mutations in infants}}, url = {{http://dx.doi.org/10.1128/jvi.00072-24}}, doi = {{10.1128/jvi.00072-24}}, volume = {{98}}, year = {{2024}}, }