Killer immunoglobulin-like receptors and HLA act both independently and synergistically to modify HIV disease progression

Gaudieri, Silvana; DeSantis, David; McKinnon, E.; Moore, Crystal Dea; Nolan, David; Witt, Campbell S.; Mallal, S.; Christiansen, Frank

doi:10.1038/sj.gene.6364256

Cited by 117 publications

(106 citation statements)

References 40 publications

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“…This would be consistent with the interaction between KIR2DL3 and C1-group HLA-C alleles being relatively weak compared to the alternative combinations KIR2DL2 + C1 and KIR2D1 + C2 (Moesta, Norman et al 2008). Furthermore, other HLA-C and KIR as well as HLA-B and the 3D KIR gene interactions are also likely to be involved in HCV resolution as has been shown for HIV infection (Gaudieri, DeSantis et al 2005).…”

Section: Nk Cell Kirs and Hla Ligandssupporting

confidence: 65%

Genetic Variation of Host Immune Response Genes and Their Effect on Hepatitis C Infection and Treatment Outcome

Deshpande¹,

Lucas²,

Gaudieri³

2012

Analysis of Genetic Variation in Animals

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Section: Nk Cell Kirs and Hla Ligandssupporting

confidence: 65%

Genetic Variation of Host Immune Response Genes and Their Effect on Hepatitis C Infection and Treatment Outcome

Deshpande¹,

Lucas²,

Gaudieri³

2012

Analysis of Genetic Variation in Animals

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“…Moreover, epidemiological studies have shown that adult individuals with the KIR3DS1 gene and at least one HLA allele from the public Bw4 epitope bearing an isoleucine at position 80 (HLA-Bw4 Ile80 ) may have slower progression to AIDS (4,33). Importantly, other reports could not confirm the same effect (34,35). However, the study by Gaudieri et al still showed associations between both HLA and the KIR genotype and the outcome of HIV-1 infection (35).…”

mentioning

confidence: 42%

“…Importantly, other reports could not confirm the same effect (34,35). However, the study by Gaudieri et al still showed associations between both HLA and the KIR genotype and the outcome of HIV-1 infection (35). Moreover, recent studies have shown that KIR and HLA interactions can affect the risk of HIV-1 transmission and specifically that KIR3DS1 expression triggers NK cell activation (36,37).…”

mentioning

confidence: 61%

Natural Killer Cells in Perinatally HIV-1-Infected Children Exhibit Less Degranulation Compared to HIV-1-Exposed Uninfected Children and Their Expression of KIR2DL3, NKG2C, and NKp46 Correlates with Disease Severity

Ballan

Long

et al. 2007

The Journal of Immunology

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NK cells play an integral role in the innate immune response by targeting virally infected and transformed cells with direct killing and providing help to adaptive responses through cytokine secretion. Whereas recent studies have focused on NK cells in HIV-1-infected adults, the role of NK cells in perinatally HIV-1-infected children is less studied. Using multiparametric flow cytometric analysis, we assessed the number, phenotype, and function of NK cell subsets in the peripheral blood of perinatally HIV-1-infected children on highly active antiretroviral therapy and compared them to perinatally exposed but uninfected children. We observed an increased frequency of NK cells expressing inhibitory killer Ig-like receptors in infected children. This difference existed despite comparable levels of total NK cells and NK cell subpopulations between the two groups. Additionally, NK cell subsets from infected children expressed, with and without stimulation, significantly lower levels of the degranulation marker CD107, which correlates with NK cell cytotoxicity. Lastly, increased expression of KIR2DL3, NKG2C, and NKp46 on NK cells correlated with decreased CD4+ T-lymphocyte percentage, an indicator of disease severity in HIV-1- infected children. Taken together, these results show that HIV-1-infected children retain a large population of cytotoxically dysfunctional NK cells relative to perinatally exposed uninfected children. This reduced function appears concurrently with distinct NK cell surface receptor expression and is associated with a loss of CD4+ T cells. This finding suggests that NK cells may have an important role in HIV-1 disease pathogenesis in HIV-1-infected children.

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“…We may speculate that the KIR, which are expressed on natural killer (NK) cells are likely candidates for the type of MHC receptors referred to above. Several reports have demonstrated that the presence of specific KIR-MHC pairs influence HIVinduced disease progression, [43][44][45] the onset of opportunistic infections in HIV-infected patients 46 and the probability of becoming HIV infected. 47 Results from ex vivo viral replication assays in SIV-infected rhesus macaques showed that NK cells can suppress viral replication substantially but to a variable extent.…”

Section: Discussionmentioning

confidence: 99%

Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques

Sauermann

Siddiqui

et al. 2007

Genes Immun

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In both human immunodeficiency virus-infected humans and simian immunodeficiency virus (SIV)-infected macaques, genes encoded in the major histocompatibility complex (MHC) class I region are important determinants of disease progression. However, compared to the human human lymphocyte antigen complex, the macaque MHC region encodes many more class I genes. Macaques with the same immunodominant class I genes express additional Mhc genes with the potential to influence the disease course. We therefore assessed the association between of the Mhc class I haplotypes, rather than single gene variants, and survival time in SIV-infected rhesus macaques (Macaca mulatta). DNA sequence analysis and Mhc genotyping of 245 pedigreed monkeys identified 17 Mhc class I haplotypes that constitute 10 major genotypes. Among 81 vaccination-naive, SIV-infected macaques, 71 monkeys carried at least one Mhc class I haplotype encoding only MHC antigens that were incapable of inducing an effective anti-SIV cytotoxic T lymphocytes response. Study of these macaques enabled us to relate individual Mhc class I haplotypes to slow, medium and rapid disease progression. In a post hoc analysis, classification according to disease progression was found to explain at least 48% of the observed variation of survival time.

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Killer immunoglobulin-like receptors and HLA act both independently and synergistically to modify HIV disease progression

Cited by 117 publications

References 40 publications

Genetic Variation of Host Immune Response Genes and Their Effect on Hepatitis C Infection and Treatment Outcome

Genetic Variation of Host Immune Response Genes and Their Effect on Hepatitis C Infection and Treatment Outcome

Natural Killer Cells in Perinatally HIV-1-Infected Children Exhibit Less Degranulation Compared to HIV-1-Exposed Uninfected Children and Their Expression of KIR2DL3, NKG2C, and NKp46 Correlates with Disease Severity

Mhc class I haplotypes associated with survival time in simian immunodeficiency virus (SIV)-infected rhesus macaques

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