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Higher HIV-1 evolutionary rate is associated with cytotoxic T lymphocyte escape mutations in infants

Nazziwa, Jamirah LU orcid ; Andrews, Sophie M. ; Hou, Mimi M. LU ; Bruhn, Christian A.W. LU ; Garcia-Knight, Miguel A. ; Slyker, Jennifer ; Hill, Sarah ; Payne, Barbara Lohman ; Moringas, Dorothy and Lemey, Philippe , et al. (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.

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organization
publishing date
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
  • scopus:85199813086
  • pmid:38814066
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}},
}