Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS

Boswell, M. T.; Nazziwa, J.; Kuroki, K.; Palm, A.; Karlson, S.; Månsson, F.; Biague, A.; da Silva, Z. J.; Onyango, C. O.; de Silva, T. I.; Jaye, A.; Norrgren, H.; Medstrand, P.; Jansson, M.; Maenaka, K.; Rowland-Jones, S. L.; Esbjörnsson, J.

Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS

Mark

Boswell, M. T. ^LU ; Nazziwa, J. ^LU

; Kuroki, K. ; Palm, A. ^LU ; Karlson, S. ^LU

; Månsson, F. ^LU ; Biague, A. ; da Silva, Z. J. ; Onyango, C. O. and de Silva, T. I. , et al. (2022) In Virus Evolution 8(2).

Abstract: HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26... (More); HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10^-3 versus 1.4x10^-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors – synonymous rates: 4.6x10^-3 vs. 2.3x10^-3; and nonsynonymous rates: 6.9x10^-4 vs. 2.7x10^-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.
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Please use this url to cite or link to this publication: https://lup.lub.lu.se/record/ea84106b-d74a-4f31-b147-4b0eea21e5d1

author

Boswell, M. T. ^LU ; Nazziwa, J. ^LU

; Kuroki, K. ; Palm, A. ^LU ; Karlson, S. ^LU

; Månsson, F. ^LU ; Biague, A. ; da Silva, Z. J. ; Onyango, C. O. and de Silva, T. I. , et al. (More)

Boswell, M. T. ^LU ; Nazziwa, J. ^LU

; Kuroki, K. ; Palm, A. ^LU ; Karlson, S. ^LU

; Månsson, F. ^LU ; Biague, A. ; da Silva, Z. J. ; Onyango, C. O. ; de Silva, T. I. ; Jaye, A. ; Norrgren, H. ^LU ; Medstrand, P. ^LU

; Jansson, M. ^LU ; Maenaka, K. ; Rowland-Jones, S. L. and Esbjörnsson, J. ^LU

(Less)

author collaboration

SWEGUB CORE group

organization

publishing date

2022-10-01

type

Contribution to journal

publication status

published

subject

Infectious Medicine

keywords

capsid, evolution, HIV-2, p26

in

Virus Evolution

volume

8

issue

2

article number

veac075

publisher

Oxford University Press

external identifiers

pmid:36533148
scopus:85159617627

ISSN

2057-1577

DOI

10.1093/ve/veac075

language

English

LU publication?

yes

id

ea84106b-d74a-4f31-b147-4b0eea21e5d1

date added to LUP

2023-09-25 14:47:29

date last changed

2024-04-19 01:38:58

@article{ea84106b-d74a-4f31-b147-4b0eea21e5d1,
  abstract     = {{<p>HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10<sup>-3</sup> versus 1.4x10<sup>-3</sup> base substitutions per site, P&lt;0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors – synonymous rates: 4.6x10<sup>-3</sup> vs. 2.3x10<sup>-3</sup>; and nonsynonymous rates: 6.9x10<sup>-4</sup> vs. 2.7x10<sup>-4</sup> substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.</p>}},
  author       = {{Boswell, M. T. and Nazziwa, J. and Kuroki, K. and Palm, A. and Karlson, S. and Månsson, F. and Biague, A. and da Silva, Z. J. and Onyango, C. O. and de Silva, T. I. and Jaye, A. and Norrgren, H. and Medstrand, P. and Jansson, M. and Maenaka, K. and Rowland-Jones, S. L. and Esbjörnsson, J.}},
  issn         = {{2057-1577}},
  keywords     = {{capsid; evolution; HIV-2; p26}},
  language     = {{eng}},
  month        = {{10}},
  number       = {{2}},
  publisher    = {{Oxford University Press}},
  series       = {{Virus Evolution}},
  title        = {{Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS}},
  url          = {{http://dx.doi.org/10.1093/ve/veac075}},
  doi          = {{10.1093/ve/veac075}},
  volume       = {{8}},
  year         = {{2022}},
}

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Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS