Influence of sickle cell disease on susceptibility to HIV infection.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2020
Historique:
received: 28 01 2019
accepted: 11 06 2019
entrez: 9 4 2020
pubmed: 9 4 2020
medline: 9 7 2020
Statut: epublish

Résumé

People with sickle cell disease (SCD) are reported to have low rates of HIV infection, slower progression to AIDS and lower HIV-associated mortality compared to the general population. Mechanisms of potential resistance to HIV in SCD are incompletely understood. We retrospectively reviewed the Transfusion Safety Study to compare HIV status between people with SCD and other congenital anemias who were routinely exposed to blood products during the high-risk period before HIV screening implementation. Non-SCD congenital anemia diagnosis was associated with a higher risk of HIV acquisition compared to SCD (OR 13.1 95%CI 1.6-108.9). In addition, we prospectively enrolled 30 SCD cases and 30 non-SCD controls to investigate potential mechanisms of resistance to HIV in SCD. CCR5 and CCR7 expression was lower and CD4 expression was higher on CD4+ T cells from SCD cases compared to controls. Surface expression of CD4+ T cell CXCR4, CD38 and HLA-DR did not differ between the groups. SCD CD4+ T cells were not less susceptible to HIV infection than controls. Levels of multiple cytokines were elevated in the SCD plasma, but SCD plasma compared to control plasma did not inhibit HIV infection of target cells. In conclusion, our epidemiological data support people with SCD being resistant to HIV infection. Potential mechanisms include lower CD4+ T cell expression of CCR5 and CCR7, balanced by increased CD4 expression and cytokine levels, which did not result in in vitro resistance to HIV infection. Further study is needed to define the risk and pathophysiology of HIV in persons with SCD.

Identifiants

pubmed: 32267841
doi: 10.1371/journal.pone.0218880
pii: PONE-D-19-02618
pmc: PMC7141606
doi:

Substances chimiques

Cytokines 0

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0218880

Subventions

Organisme : NHLBI NIH HHS
ID : HHSN268201100007I
Pays : United States

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Shannon Kelly (S)

Vitalant Research Institute, San Francisco, CA, United States of America.
UCSF Benioff Children's Hospital Oakland, Oakland, CA, United States of America.

Evan S Jacobs (ES)

Vitalant Research Institute, San Francisco, CA, United States of America.

Mars Stone (M)

Vitalant Research Institute, San Francisco, CA, United States of America.

Sheila M Keating (SM)

Vitalant Research Institute, San Francisco, CA, United States of America.

Tzong-Hae Lee (TH)

Vitalant Research Institute, San Francisco, CA, United States of America.

Daniel Chafets (D)

Vitalant Research Institute, San Francisco, CA, United States of America.

John Heitman (J)

Vitalant Research Institute, San Francisco, CA, United States of America.

Melanie Dimapasoc (M)

Vitalant Research Institute, San Francisco, CA, United States of America.

Eva Operskalski (E)

Keck School of Medicine, University of Southern California, Los Angeles, CA, United States of America.

Ward Hagar (W)

UCSF Benioff Children's Hospital Oakland, Oakland, CA, United States of America.

Elliott Vichinsky (E)

UCSF Benioff Children's Hospital Oakland, Oakland, CA, United States of America.

Michael P Busch (MP)

Vitalant Research Institute, San Francisco, CA, United States of America.

Philip J Norris (PJ)

Vitalant Research Institute, San Francisco, CA, United States of America.

Brian Custer (B)

Vitalant Research Institute, San Francisco, CA, United States of America.

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Classifications MeSH