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Activating Killer Immunoglobulin Receptors and HLA-C: a successful combination providing HIV-1 control

View Article: PubMed Central - PubMed

ABSTRACT

Several studies demonstrated a relevant role of polymorphisms located within the HLA-B and -C loci and the Killer Immunoglobulin Receptors (KIRs) 3DL1 and 3DS1 in controlling HIV-1 replication. KIRs are regulatory receptors expressed at the surface of NK and CD8+ T-cells that specifically bind HLA-A and -B alleles belonging to the Bw4 supratype and all the -C alleles expressing the C1 or C2 supratype. We here disclose a novel signature associated with the Elite Controller but not with the long-term nonprogressor status concerning 2DS activating KIRs and HLA-C2 alleles insensitive to miRNA148a regulation. Overall, our findings support a crucial role of NK cells in the control of HIV-1 viremia.

No MeSH data available.


Principal component analysis of genetic markers on chromosome 19 (A) or 6 (B). Distinct groups of HIV-1 infected individuals and HIV-1 negative donors are indicated with a black filled box (E: Elite Controller, L: Long Term Non Progressor, P: Progressor, H: Healthy HIV-1 negative donors). (A) KIR genotypes are shown by black filled circles (p: positive, n: negative). (B) HLA-C, HLA-Bw4-I80, −35 SNPs and miRNA148a SNPs homozygous and- heterozygous genotypes are indicated.
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f1: Principal component analysis of genetic markers on chromosome 19 (A) or 6 (B). Distinct groups of HIV-1 infected individuals and HIV-1 negative donors are indicated with a black filled box (E: Elite Controller, L: Long Term Non Progressor, P: Progressor, H: Healthy HIV-1 negative donors). (A) KIR genotypes are shown by black filled circles (p: positive, n: negative). (B) HLA-C, HLA-Bw4-I80, −35 SNPs and miRNA148a SNPs homozygous and- heterozygous genotypes are indicated.

Mentions: An explorative multiple correspondence analysis of selected chromosome 6 polymorphisms within the HLA-B and -C class I region and of KIR genes was conducted independently to verify whether combinations of the selected chromosome 6 and 19 markers could discriminate between the two best characterized cohorts of natural controller of HIV-1 infection, i.e. EC and LTNP, in comparison to HIV-1 Progressors (P) or HIV-1 seronegative healthy blood donors (HD). The presence of activating KIR genes, namely 3DS1, 2DS1 and 2DS5 on chromosome 19 (Fig. 1A) clearly distinguished the 40 EC (lower right quadrant) from the 111 HD (upper left quadrant) and to some extent from the189 HIV P (lower left quadrant), whereas the 39 LTNP segregated in an intermediate position between EC and P.


Activating Killer Immunoglobulin Receptors and HLA-C: a successful combination providing HIV-1 control
Principal component analysis of genetic markers on chromosome 19 (A) or 6 (B). Distinct groups of HIV-1 infected individuals and HIV-1 negative donors are indicated with a black filled box (E: Elite Controller, L: Long Term Non Progressor, P: Progressor, H: Healthy HIV-1 negative donors). (A) KIR genotypes are shown by black filled circles (p: positive, n: negative). (B) HLA-C, HLA-Bw4-I80, −35 SNPs and miRNA148a SNPs homozygous and- heterozygous genotypes are indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5304173&req=5

f1: Principal component analysis of genetic markers on chromosome 19 (A) or 6 (B). Distinct groups of HIV-1 infected individuals and HIV-1 negative donors are indicated with a black filled box (E: Elite Controller, L: Long Term Non Progressor, P: Progressor, H: Healthy HIV-1 negative donors). (A) KIR genotypes are shown by black filled circles (p: positive, n: negative). (B) HLA-C, HLA-Bw4-I80, −35 SNPs and miRNA148a SNPs homozygous and- heterozygous genotypes are indicated.
Mentions: An explorative multiple correspondence analysis of selected chromosome 6 polymorphisms within the HLA-B and -C class I region and of KIR genes was conducted independently to verify whether combinations of the selected chromosome 6 and 19 markers could discriminate between the two best characterized cohorts of natural controller of HIV-1 infection, i.e. EC and LTNP, in comparison to HIV-1 Progressors (P) or HIV-1 seronegative healthy blood donors (HD). The presence of activating KIR genes, namely 3DS1, 2DS1 and 2DS5 on chromosome 19 (Fig. 1A) clearly distinguished the 40 EC (lower right quadrant) from the 111 HD (upper left quadrant) and to some extent from the189 HIV P (lower left quadrant), whereas the 39 LTNP segregated in an intermediate position between EC and P.

View Article: PubMed Central - PubMed

ABSTRACT

Several studies demonstrated a relevant role of polymorphisms located within the HLA-B and -C loci and the Killer Immunoglobulin Receptors (KIRs) 3DL1 and 3DS1 in controlling HIV-1 replication. KIRs are regulatory receptors expressed at the surface of NK and CD8+ T-cells that specifically bind HLA-A and -B alleles belonging to the Bw4 supratype and all the -C alleles expressing the C1 or C2 supratype. We here disclose a novel signature associated with the Elite Controller but not with the long-term nonprogressor status concerning 2DS activating KIRs and HLA-C2 alleles insensitive to miRNA148a regulation. Overall, our findings support a crucial role of NK cells in the control of HIV-1 viremia.

No MeSH data available.