Rapid progression is associated with lymphoid follicle dysfunction in SIV-infected infant rhesus macaques.
Animals
B-Lymphocytes
/ immunology
Disease Progression
Genetic Variation
Germinal Center
/ immunology
Humans
Immunity, Humoral
Interferon Type I
/ immunology
Lymphoid Tissue
/ immunology
Macaca mulatta
Phenotype
Simian Acquired Immunodeficiency Syndrome
/ immunology
Simian Immunodeficiency Virus
/ genetics
Viral Load
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
05 2021
05 2021
Historique:
received:
07
01
2021
accepted:
20
04
2021
revised:
19
05
2021
pubmed:
8
5
2021
medline:
13
10
2021
entrez:
7
5
2021
Statut:
epublish
Résumé
HIV-infected infants are at an increased risk of progressing rapidly to AIDS in the first weeks of life. Here, we evaluated immunological and virological parameters in 25 SIV-infected infant rhesus macaques to understand the factors influencing a rapid disease outcome. Infant macaques were infected with SIVmac251 and monitored for 10 to 17 weeks post-infection. SIV-infected infants were divided into either typical (TypP) or rapid (RP) progressor groups based on levels of plasma anti-SIV antibody and viral load, with RP infants having low SIV-specific antibodies and high viral loads. Following SIV infection, 11 out of 25 infant macaques exhibited an RP phenotype. Interestingly, TypP had lower levels of total CD4 T cells, similar reductions in CD4/CD8 ratios and elevated activation of CD8 T cells, as measured by the levels of HLA-DR, compared to RP. Differences between the two groups were identified in other immune cell populations, including a failure to expand activated memory (CD21-CD27+) B cells in peripheral blood in RP infant macaques, as well as reduced levels of germinal center (GC) B cells and T follicular helper (Tfh) cells in spleens (4- and 10-weeks post-SIV). Reduced B cell proliferation in splenic germinal GCs was associated with increased SIV+ cell density and follicular type 1 interferon (IFN)-induced immune activation. Further analyses determined that at 2-weeks post SIV infection TypP infants exhibited elevated levels of the GC-inducing chemokine CXCL13 in plasma, as well as significantly lower levels of viral envelope diversity compared to RP infants. Our findings provide evidence that early viral and immunologic events following SIV infection contributes to impairment of B cells, Tfh cells and germinal center formation, ultimately impeding the development of SIV-specific antibody responses in rapidly progressing infant macaques.
Identifiants
pubmed: 33961680
doi: 10.1371/journal.ppat.1009575
pii: PPATHOGENS-D-21-00023
pmc: PMC8133453
doi:
Substances chimiques
Interferon Type I
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009575Subventions
Organisme : NIAID NIH HHS
ID : R01 AI133706
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE023047
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE026336
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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