Innate and adaptive immunity in long-term non-progression in HIV disease

Long-term non-progressors (LTNP) were identified after 10-15 years of the epidemic, and have been the subject of intense investigation ever since. In a small minority of cases, infection with nef/3'LTR deleted attenuated viral strains allowed control over viral replication. A common feature of...

Full description

Bibliographic Details
Main Authors: John eZaunders, David evan Bockel
Format: Article
Language:English
Published: Frontiers Media S.A. 2013-04-01
Series:Frontiers in Immunology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00095/full
_version_ 1818009185688748032
author John eZaunders
David evan Bockel
author_facet John eZaunders
David evan Bockel
author_sort John eZaunders
collection DOAJ
description Long-term non-progressors (LTNP) were identified after 10-15 years of the epidemic, and have been the subject of intense investigation ever since. In a small minority of cases, infection with nef/3'LTR deleted attenuated viral strains allowed control over viral replication. A common feature of LTNP is the readily detected proliferation of CD4 T cells in vitro, in response to p24. In some cases, the responding CD4 T cells have cytotoxic effector function and may target conserved p24 epitopes, similar to the CD8 T cells described below. LTNP may also carry much lower HIV DNA burden in key CD4 subsets, presumably resulting from lower viral replication during primary infection. Some studies, but not others, suggest that LTNP have CD4 T cells that are relatively resistant to HIV infection in vitro. One possible mechanism may involve up-regulation of the cell cycle regulator p21/waf in CD4 T cells from LTNP. Delayed progression in Caucasian LTNP is also partly associated with heterozygosity of the ∆32 CCR5 allele, probably through decreased expression of CCR5 co-receptor on CD4 T cells. However, in approximately half of Caucasian LTNP, two host genotypes, namely HLA-B57 and HLA-B27, are associated with viral control. Immunodominant CD8 T cells from these individuals target epitopes in p24 that are highly conserved, and escape mutations have significant fitness costs to the virus. Furthermore, recent studies have suggested that these CD8 T cells from LTNP, but not from HLA-B27 or HLA-B57 progressors, can cross-react with intermediate escape mutations, preventing full escape via compensatory mutations. Humoral immunity appears to play little part in LTNP subjects, since broadly neutralizing antibodies are rare, even amongst slow progressors. Recent genome wide comparisons between LTNP and progressors have confirmed the HLA-B57, HLA-B27 and delta32 CCR5 allelic associations, plus indicated a role for HLA-C/KIR interactions, but have not revealed any new genotypes so far.
first_indexed 2024-04-14T05:39:42Z
format Article
id doaj.art-d8343a4b3f3d40babace981338df731b
institution Directory Open Access Journal
issn 1664-3224
language English
last_indexed 2024-04-14T05:39:42Z
publishDate 2013-04-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Immunology
spelling doaj.art-d8343a4b3f3d40babace981338df731b2022-12-22T02:09:31ZengFrontiers Media S.A.Frontiers in Immunology1664-32242013-04-01410.3389/fimmu.2013.0009551485Innate and adaptive immunity in long-term non-progression in HIV diseaseJohn eZaunders0David evan Bockel1St Vincent's Hospital, SydneyKirby InstituteLong-term non-progressors (LTNP) were identified after 10-15 years of the epidemic, and have been the subject of intense investigation ever since. In a small minority of cases, infection with nef/3'LTR deleted attenuated viral strains allowed control over viral replication. A common feature of LTNP is the readily detected proliferation of CD4 T cells in vitro, in response to p24. In some cases, the responding CD4 T cells have cytotoxic effector function and may target conserved p24 epitopes, similar to the CD8 T cells described below. LTNP may also carry much lower HIV DNA burden in key CD4 subsets, presumably resulting from lower viral replication during primary infection. Some studies, but not others, suggest that LTNP have CD4 T cells that are relatively resistant to HIV infection in vitro. One possible mechanism may involve up-regulation of the cell cycle regulator p21/waf in CD4 T cells from LTNP. Delayed progression in Caucasian LTNP is also partly associated with heterozygosity of the ∆32 CCR5 allele, probably through decreased expression of CCR5 co-receptor on CD4 T cells. However, in approximately half of Caucasian LTNP, two host genotypes, namely HLA-B57 and HLA-B27, are associated with viral control. Immunodominant CD8 T cells from these individuals target epitopes in p24 that are highly conserved, and escape mutations have significant fitness costs to the virus. Furthermore, recent studies have suggested that these CD8 T cells from LTNP, but not from HLA-B27 or HLA-B57 progressors, can cross-react with intermediate escape mutations, preventing full escape via compensatory mutations. Humoral immunity appears to play little part in LTNP subjects, since broadly neutralizing antibodies are rare, even amongst slow progressors. Recent genome wide comparisons between LTNP and progressors have confirmed the HLA-B57, HLA-B27 and delta32 CCR5 allelic associations, plus indicated a role for HLA-C/KIR interactions, but have not revealed any new genotypes so far.http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00095/fullHIV-1cell-mediated immunitycytotoxic T lymphocytesElite ControllersLong-term non-progressors
spellingShingle John eZaunders
David evan Bockel
Innate and adaptive immunity in long-term non-progression in HIV disease
Frontiers in Immunology
HIV-1
cell-mediated immunity
cytotoxic T lymphocytes
Elite Controllers
Long-term non-progressors
title Innate and adaptive immunity in long-term non-progression in HIV disease
title_full Innate and adaptive immunity in long-term non-progression in HIV disease
title_fullStr Innate and adaptive immunity in long-term non-progression in HIV disease
title_full_unstemmed Innate and adaptive immunity in long-term non-progression in HIV disease
title_short Innate and adaptive immunity in long-term non-progression in HIV disease
title_sort innate and adaptive immunity in long term non progression in hiv disease
topic HIV-1
cell-mediated immunity
cytotoxic T lymphocytes
Elite Controllers
Long-term non-progressors
url http://journal.frontiersin.org/Journal/10.3389/fimmu.2013.00095/full
work_keys_str_mv AT johnezaunders innateandadaptiveimmunityinlongtermnonprogressioninhivdisease
AT davidevanbockel innateandadaptiveimmunityinlongtermnonprogressioninhivdisease