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Research Article | Host-Microbe Biology

Low Postseroconversion CD4+ T-cell Level Is Associated with Faster Disease Progression and Higher Viral Evolutionary Rate in HIV-2 Infection

Angelica A. Palm, Philippe Lemey, Marianne Jansson, Fredrik Månsson, Anders Kvist, Zsófia Szojka, Antonio Biague, Zacarias José da Silva, Sarah L. Rowland-Jones, Hans Norrgren, Joakim Esbjörnsson, Patrik Medstrand
Dimitrios Paraskevis, Editor
Angelica A. Palm
aDepartment of Laboratory Medicine, Lund University, Lund, Sweden
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Philippe Lemey
bDepartment of Microbiology and Immunology, Rega Institute, KU Leuven—University of Leuven, Leuven, Belgium
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Marianne Jansson
aDepartment of Laboratory Medicine, Lund University, Lund, Sweden
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Fredrik Månsson
cDepartment of Translational Medicine, Lund University, Lund, Sweden
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Anders Kvist
dDepartment of Clinical Sciences Lund, Lund University, Lund, Sweden
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Zsófia Szojka
eDepartment of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary
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Antonio Biague
fNational Public Health Laboratory, Bissau, Guinea-Bissau
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Zacarias José da Silva
fNational Public Health Laboratory, Bissau, Guinea-Bissau
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Sarah L. Rowland-Jones
gNuffield Department of Medicine, NDM Research Building, University of Oxford, Oxford, United Kingdom
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Hans Norrgren
dDepartment of Clinical Sciences Lund, Lund University, Lund, Sweden
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Joakim Esbjörnsson
aDepartment of Laboratory Medicine, Lund University, Lund, Sweden
gNuffield Department of Medicine, NDM Research Building, University of Oxford, Oxford, United Kingdom
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Patrik Medstrand
cDepartment of Translational Medicine, Lund University, Lund, Sweden
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Dimitrios Paraskevis
Medical School, University of Athens
Roles: Editor
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DOI: 10.1128/mBio.01245-18
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ABSTRACT

A positive correlation between virus evolutionary rate and disease progression has been shown for human immunodeficiency virus type 1 (HIV-1) infection. Much less is known about HIV-2, the second causative agent of AIDS. We analyzed 528 HIV-2 env V1-C3 sequences generated from longitudinal plasma samples that were collected from 16 study participants during a median observation time of 7.9 years (interquartile range [IQR], 5.2 to 14.0 years). Study participants were classified as faster or slower disease progressors based on longitudinal CD4+ T-cell data. The HIV-2 evolutionary rate was significantly associated with CD4+ T-cell levels and was almost twice as high among the faster progressors as among the slower progressors. Higher evolutionary rates were accounted for by both synonymous and nonsynonymous nucleotide substitutions. Moreover, slow disease progression was associated with stronger positive selection on HIV-2/SIVsm (simian immunodeficiency virus infecting sooty mangabey) surface-exposed conserved residues. This study demonstrated a number of previously unknown characteristics linking HIV-2 disease progression with virus evolution. Some of these findings distinguish HIV-2 from HIV-1 and may contribute to the understanding of differences in pathogenesis.

IMPORTANCE The relationship between HIV evolution and disease progression is fundamental to our understanding of HIV immune control and vaccine design. There are no clear definitions for faster and slower HIV-2 disease progression and for the relationship of the rate of progression with HIV-2 evolution. To address the hypothesis that viral evolution is correlated with disease progression in HIV-2 infection, we determined faster and slower disease progression based on follow-up data from a prospective cohort of police officers in Guinea-Bissau. The analysis showed that although the CD4+ T-cell level and the decline in the level were independently associated with progression to AIDS, only the CD4+ T-cell level or a combined CD4+ T-cell level/decline stratification was associated with the rate of HIV-2 evolution. The HIV-2 evolutionary rate was almost twice as high among the faster progressors as among the slower progressors. Importantly, this report defines previously unknown characteristics linking HIV-2 disease progression with virus evolution.

  • Copyright © 2019 Palm et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

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Low Postseroconversion CD4+ T-cell Level Is Associated with Faster Disease Progression and Higher Viral Evolutionary Rate in HIV-2 Infection
Angelica A. Palm, Philippe Lemey, Marianne Jansson, Fredrik Månsson, Anders Kvist, Zsófia Szojka, Antonio Biague, Zacarias José da Silva, Sarah L. Rowland-Jones, Hans Norrgren, Joakim Esbjörnsson, Patrik Medstrand for the SWEGUB CORE Group
mBio Jan 2019, 10 (1) e01245-18; DOI: 10.1128/mBio.01245-18

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Low Postseroconversion CD4+ T-cell Level Is Associated with Faster Disease Progression and Higher Viral Evolutionary Rate in HIV-2 Infection
Angelica A. Palm, Philippe Lemey, Marianne Jansson, Fredrik Månsson, Anders Kvist, Zsófia Szojka, Antonio Biague, Zacarias José da Silva, Sarah L. Rowland-Jones, Hans Norrgren, Joakim Esbjörnsson, Patrik Medstrand for the SWEGUB CORE Group
mBio Jan 2019, 10 (1) e01245-18; DOI: 10.1128/mBio.01245-18
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KEYWORDS

disease progression
human immunodeficiency virus
viral evolution

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