Associations of human leukocyte antigen-G with resistance and susceptibility to HIV-1 infection in the Pumwani sex worker cohort

Abstract

Our study showed that specific HLA-G alleles are associated with resistance or susceptibility to HIV-1 acquisition in this high-risk population. Further studies are needed to understand its functional significance in HIV-1 transmission.

Maternal human leukocyte antigen-G (HLA-G) genetic variants associate with in utero mother-to-child transmission of HIV-1 in Black South Africans

“…In one study G*01:01:01 was significantly enriched in HIV-1 resistant sex workers, whereas G*01:04:04 was significantly associated with susceptibility to HIV-1 infection (Turk et al, 2013). However in Zimbabwean women, G*01:01:08 was associated with an increased risk of HIV-1 infection, while G*01:05N offered protection from heterosexual HIV-1 infection (Matte et al, 2004).…”

“…Exons 2, 3 and 4 of HLA-G were amplified and sequenced using previously published primers (Turk et al, 2013, Hviid et al, 1997). Briefly, a 994-bp fragment encompassing exons 2 and 3 was amplified using primers HLAG_2/3PCRF (5’-CGGCCCCTGCGCGGAGGAGGGAGGGG-3’) and HLAG_2/3PCRR (5’-TCAGGACCAGAGGGAGGGCGATATTC-3’); primers HLAG_4PCRF (5’-AGGTGCTG-CTGGAGTGTC-3’) and HLAG_4PCRR (5’-TCTGGGAAAGGAGGTGAAG-3’) were used to amplify a 463-bp fragment spanning exon 4 (Turk et al, 2013). Thermocycling conditions were: 94°C for 2 min followed by 35 cycles of 94°C for 30 sec, 61.5°C/60°C for 30 sec (for exons 2-3 and exon 4, respectively) and 72°C for 1 min followed by a final extension step of 72°C for 7 min.…”

“…Thermocycling conditions were: 94°C for 2 min followed by 35 cycles of 94°C for 30 sec, 61.5°C/60°C for 30 sec (for exons 2-3 and exon 4, respectively) and 72°C for 1 min followed by a final extension step of 72°C for 7 min. PCR amplicons were purified using the Invitek MSB Spin PCRapace cleanup kit (Berlin, Germany) and sequenced in both directions by capillary electrophoresis using an ABI 3100 Genetic Analyzer (Applied Biosystems, Foster City, California, USA) with the sequencing primers described by Turk et al (2013): HLAG_2SEQR (5’-TCGTGATCTGCGCCCTG-3’); HLAG_3SEQF (5’-TGGGCGGGGCTGACCGAGGGGGTGGG-3’); HLAG_3SEQR (5’-TCAGGACCAGAG-GGAGGGCGATATTC-3’); HLAG_4SEQF (5’-GTGCTTGAATT-TTCTGACTCTT-3’) and HLAG_4SEQR (5’-TGCTTTCCCTAACAGACATGAT-3’). HLAG_2SEQF (5’-CTCCATGAGGTATTTCAGC[G]-3’) was an in-house primer designed using HLA-G intron 1 alignments and synthesised with a lock nucleic acid (LNA) modified 3’ end (indicated in square brackets).…”

“…Moreover G*01:03- alleles, which reportedly translate into lower plasma sHLA-G, were associated with a reduced risk of vertical transmission of HIV-1 (Luo et al, 2013). Whereas, in the context of sexual transmission, G*01:04:04 , an allele with reportedly higher levels of plasma sHLA-G, was associated with susceptibility to HIV-1 infection (Turk et al, 2013). Of note, amongst all these studies, few have assessed the roles of HLA-G alleles and 3’UTR SNPs collectively.…”

Human Leukocyte Antigen (HLA) and Immune Regulation: How Do Classical and Non-Classical HLA Alleles Modulate Immune Response to Human Immunodeficiency Virus and Hepatitis C Virus Infections?

“…HLA-G*01:05N increases in HIV infection, which may be due to lack of HLA-G1 and HLA-G5 expression resulting in compensation by other HLA-G isoforms, which then may inhibit NK cell activation (263). It has also been shown that the HLA-G*01:01:01 genotype is significantly enriched in HIV-resistant women, while HLA-G*01:04:04 is associated with increased rates of seroconversion (264). …”