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RESEARCH PRODUCT

Role of APOBEC3H in the Viral Control of HIV Elite Controller Patients

Norma RallónRosario Palacios-muñozMiguel GórgolasJulia HillungClara RestrepoEzequiel Ruiz-mateosRafael SanjuánAgathe LeónJosé M. CuevasJosé M. Benito

subject

AdultCD4-Positive T-LymphocytesMalers139297HIV InfectionsSingle-nucleotide polymorphismBiologyVirus ReplicationPolymorphism Single NucleotideAPOBEC3H polymorphisms03 medical and health sciencessymbols.namesake0302 clinical medicineGene FrequencyAminohydrolasesGenotypeHumansAlleleGenotypingGeneSanger sequencingCloningelite controllers.HaplotypeHIVGeneral MedicineMiddle AgedCross-Sectional StudiesHaplotypesImmunologyrs79323350symbolsFemaleResearch Paper030215 immunology

description

Background APOBEC3H (A3H) gene presents variation at 2 positions (rs139297 and rs79323350) leading to a non-functional protein. So far, there is no information on the role played by A3H in spontaneous control of HIV. The aim of this study was to evaluate the A3H polymorphisms distribution in a well-characterized group of Elite Controller (EC) subjects. Methods We analyzed the genotype distribution of two different SNPs (rs139297 and rs79323350) of A3H in 30 EC patients and compared with 11 non-controller (NC) HIV patients. Genotyping was performed by PCR, cloning and Sanger sequencing. Both polymorphisms were analyzed jointly in order to adequately attribute the active or inactive status of A3H protein. Results EC subjects included in this study were able to maintain a long-term sustained spontaneous HIV-viral control and optimal CD4-T-cell counts; however, haplotypes leading to an active protein were very poorly represented in these patients. We found that the majority of EC subjects (23/30; 77%) presented allelic combinations leading to an inactive A3H protein, a frequency slightly lower than that observed for NC studied patients (10/11; 91%). Conclusions The high prevalence of non-functional protein coding-genotypes in EC subjects seems to indicate that other innate restriction factors different from APOBEC3H could be implicated in the replication control exhibited by these subjects.

https://doi.org/10.7150/ijms.22317