Int J Med Sci 2018; 15(2):95-100. doi:10.7150/ijms.22317

Research Paper

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

José M. Benito1,2*✉, Julia Hillung3*, Clara Restrepo1,2, José M. Cuevas3,4, Agathe León5, Ezequiel Ruiz-Mateos6, Rosario Palacios-Muñoz7, Miguel Górgolas8, Rafael Sanjuán3,4#, Norma Rallón1,2#✉ On behalf of ECRIS integrated in the Spanish AIDS Research Network

1. Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Universidad Autónoma de Madrid (IIS-FJD, UAM), Spain;
2. Hospital Universitario Rey Juan Carlos, Móstoles, Spain;
3. Institute for Integrative Systems Biology (I2SysBio), Universitat de València and Consejo Superior de Investigaciones Científicas, València, Spain;
4. Departament de Genètica, Universitat de València, València, Spain;
5. Hospital Clínic of Barcelona, IDIBAPS, Barcelona, Spain;
6. Biomedicine Institute of Seville (IBiS), Sevilla, Spain;
7. Unidad de E. Infecciosas. Hospital Virgen de la Victoria e IBIMA, Málaga, Spain;
8. Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain.
* These authors contributed equally to this work
# These authors contributed equally to this work
§ The clinical centers and research groups that contribute to ECRIS are shown in Supplementary Text S1.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
Benito JM, Hillung J, Restrepo C, Cuevas JM, León A, Ruiz-Mateos E, Palacios-Muñoz R, Górgolas M, Sanjuán R, Rallón N. Role of APOBEC3H in the Viral Control of HIV Elite Controller Patients. Int J Med Sci 2018; 15(2):95-100. doi:10.7150/ijms.22317. Available from

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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.

Keywords: APOBEC3H polymorphisms, rs139297, rs79323350, HIV, elite controllers.