Analysis of polymorphism of the APOBEC3G gene in HIV positive patients




HIV; Hepatitis B; Hepatitis C; APOBEC-3G deaminase; Genetic polymorphism.


Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of the current AIDS pandemic. Viral hepatitis B (HBV) and C (HCV) are highly prevalent in HIV-infected individuals. APOBEC3G (A3G) gene is a human genetic factor currently investigated in control of HIV-1 replication and progression of AIDS. Studies investigated its effect on HCV and HBV replication. APOBEC3G mediates changes that result in loss of genetic information and production of largely defective virions in the subsequent replication cycle. APOBEC3G gene variants have been described. The H186R variant may alter APOBEC3G function or levels of expression by altering its interaction with other proteins, or modifying its editing functions. This study aims to determine the frequency of the H186R polymorphism among 324 HIV-1 positive patients with and without co-infection by hepatitis B and C and analyze the correlation of the H186R genotypes with viral load of HIV-1. The results showed AA:AG:GG genotypes in the following proportion: 88.6%:9.3%:2.1% in HIV-1 mono-infected patients and 85.4%:12.4%:2.2% in HIV/HBV. The HIV/HCV co-infected patients and those with triple infection HIV/HBV/HCV showed only AA e AG genotypes, with frequencies of 90.1%:9.9% and 78.9%:21.1%, respectively. Patients with AA genotype had viral load of 37,969 ± 68,182 copies/ml and patients with AG genotype had viral load of 48,256 ± 54,186 copies/ml (p=0.180). Our results demonstrate that there is no correlation between the genotypes of APOBEC3G H186R polymorphism and viral load of HIV-1 in study population.


Aceijas, C., & Rhodes, T. (2007). Global estimates of prevalence of HCV infection among injecting drug users. International Journal on Drug Policy, 18(5), 352–358.

An, P., Bleiber, G., Duggal, P., Nelson, G., May, M., Mangeat, B., Alobwede, I., Trono, D., Vlahov, D., Donfield S., Goedert, J.J., Phair, J., Buchbinder, S., O'Brien, S.J., Telenti, A., & Winkler, C.A. (2004). APOBEC3G genetic variants and their influence on the progression to AIDS. Journal of Virology, 78(20), 11070-11076.

Bernacchi, S., Mercenne, G., Tournaire, C., Marquet, R., & Paillart, J. C. (2011). Importance of the proline-rich multimerization domain on the oligomerization and nucleic acid binding properties of HIV-1 Vif. Nucleic Acids Research, 39(6), 2404-2415.

Bizinoto, M. C., Leal, E., Diaz, R. S., & Janini, L. M. (2011). Loci Polymorphisms of the APOBEC3G Gene in HIV Type 1-Infected Brazilians. AIDS Research and Human Retroviruses, 27(2), 137-141.

Boom, R., Sol, C. J., Salimans, M. M., Jansen, C. L., Wertheim-van Dillen, P. M., & van der Noordaa, J. (1990). Rapid and simple method for purification of nucleic acids. Journal of Clinical Microbiology, 28(3), 495-503.

Bunupuradah, T., Imahashi, M., Iampornsin, T., Matsuoka, K., Iwatani, Y., Puthanakit, T., Ananworanich, J., Sophonphan, J., Mahanontharit, A., Naoe, T., Vonthanak, S., Phanuphak, P., Sugiura, W.; & PREDICT Study Team. (2012). Association of APOBEC3G genotypes and CD4 decline in Thai and Cambodian HIV-infected children with moderate immune deficiency. AIDS Research and Therapy, 9 (1), 34.

Callegari-Jacques, S. M., Grattapaglia, D., Salzano, F. M., Salamoni, S. P., Crossetti, S. G., Ferreira, M. E., & Hutz, M. H. (2003). Historical Genetics: Spatiotemporal Analysis of the Formation of the Brazilian Population. American Journal of Human Biology, 15(6), 824-834.

Colomer-Lluch, M., Ruiz, A., Moris, A., & Prado, J. G. (2018). Restriction Factors: From Intrinsic Viral Restriction to Shaping Cellular Immunity Against HIV-1. Frontiers in Immunology, 9, 2876.

Compaore, T. R., Diarra, B., Assih, M., Obiri-Yeboah, D., Soubeiga, S. T., Ouattara, A. K., Tchelougou, D., Bisseye, C., Bakouan, D. R., Compaore, I. P., Dembele, A., Djigma, W. F., & Simpore, J. (2016). HBV/HIV co-infection and APOBEC3G polymorphisms in a population from Burkina Faso. BMC Infectious Diseases, 16, 336.

De Maio, F. A., Rocco, C. A., Aulicino, P. C., Bologna, R., Mangano, A., & Sen, L. (2011). Effect of HIV-1 Vif variability on progression to pediatric AIDS and its association with APOBEC3G and CUL5 polymorphisms. Infection, Genetics and Evolution, 11(6), 1256-1262.

De Maio, F. A., Rocco, C. A., Aulicino, P. C., Bologna, R., Mangano, A., & Sen, L. (2012). APOBEC3-mediated editing in HIV type 1 from pediatric patients and its association with APOBEC3G/CUL5 polymorphisms and Vif variability. AIDS Research and Human Retroviruses, 28(6), 619-627.

Do, H., Vasilescu, A., Diop, G., Hirtzig, T., Heath, S. C., Coulonges, C., Rappaport, J., Therwath, A., Lathrop, M., Matsuda, F., & Zagury, J. F. (2005). Exhaustive genotyping of the CEM15 (APOBEC3G) gene and absence of association with AIDS progression in a French Cohort. Journal of Infectious Diseases, 191(2), 159-163.

Ezzikouri, S., Kitab, B., Rebbani, K., Marchio, A., Wain-Hobson, S., Dejean, A., Vartanian, J. P., Pineau, P., & Benjelloun, S. (2013). Polymorphic APOBEC3 modulates chronic hepatitis B in Moroccan population. Journal of Viral Hepatitis, 20(10), 678-686.

Ganesan, M., Poluektova, L. Y., Kharbanda, K. K., & Osna, N. A. (2019). Human immunodeficiency virus and hepatotropic viruses co-morbidities as the inducers of liver injury progression. World Journal of Gastroenterology, 25(4), 398-410.

He, X. T., Xu, H. Q., Wang, X. M., He, X. S., Niu, J. Q., & Gao, P. J. (2017). Association between polymorphisms of the APOBEC3G gene and chronic hepatitis B viral infection and hepatitis B virus-related hepatocellular carcinoma. World Journal of Gastroenterology, 23(2), 232-241.

Kitamura, K., Wang, Z., Chowdhury, S., Simadu, M., Koura, M., & Muramatsu, M. (2013). Uracil DNA glycosylase counteracts APOBEC3G-induced hypermutation of hepatitis B viral genomes: excision repair of covalently closed circular DNA. PLoS Pathogens, 9(5), e1003361.

Köck, J. & Blum, H. E. (2008). Hypermutation of hepatitis B virus genomes by APOBEC3G, APOBEC3C and APOBEC3H. Journal of General Virology, 89(Pt 5), 1184-1191.

Komohara, Y., Yano, H., Shichijo, S., Shimotohno, K., Itoh, K., & Yamada, A. (2006) High expression of APOBEC3G in patients infected with hepatitis C virus. Journal of Molecular Histology, 37(8-9), 327-332.

Krug, L. P., Lunge, V. R., Ikuta, N., Fonseca, A. S., Cheinquer, H., Ozaki, L. S., & Barros, S. G. (1996). Hepatitis C virus genotypes in Southern Brazil. Brazilian Journal of Medical and Biological Research, 29(12), 1629-1632.

Lins, T. C., Vieira, R. G., Abreu, B. S., Grattapaglia, D., & Pereira, R. W. (2010). Genetic composition of Brazilian population samples based on a set of twenty eight ancestry informative SNPs. American Journal of Human Biology, 22(2), 187-192.

Mangeat, B., Turelli, P., Caron, G., Friedli, M., Perrin, L., & Trono, D. (2003). Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature, 424(6944), 99-103.

Mercenne, G., Bernacchi, S., Richer, D., Bec, G., Henriet, S., Paillart, J. C., & Marquet, R. (2010). HIV-1 Vif binds to APOBEC3G mRNA and inhibits its translation. Nucleic Acids Res, 38 (2), 633-646.

Mohamadkhani, A., Pourdadash, A., Tayebi, S., Estakhri, A., Nazem, H., Sotoudeh, M., & Poustchi, H. (2012). The potential role of APOBEC3G in limiting replication of hepatitis B virus. Arab Journal of Gastroenterology, 13(4), 170-173.

Münk, C., Willemsen, A., & Bravo, I. G. (2012). An ancient history of gene duplications, fusions and losses in the evolution of APOBEC3 mutators in mammals. BMC Evolutionary Biology, 12, 71.

Nguyen, D. H., Gummuluru, S., & Hu, J. (2007). Deamination- independent inhibition of hepatitis B virus reverse transcription by APOBEC3G. Journal of Virology, 81(9), 4465-4472.

Noguchi, C., Hiraga, N., Mori, N., Tsuge, M., Imamura, M., Takahashi, S., Fujimoto, Y., Ochi, H., Abe, H., Maekawa, T., Yatsuji, H., Shirakawa, K., Takaori-Kondo, A., & Chayama, K. (2007). Dual effect of APOBEC3G on Hepatitis B virus. Journal of General Virology, 88(Pt 2), 432-440.

Norman, J. M., Mashiba, M., McNamara, L. A., Onafuwa-Nuga, A., Chiari-Fort, E., Shen, W., & Collins, K. L. (2012). The anti-viral factor APOBEC3G enhances natural killer cell recognition of HIV-infected primary T cells. Nature Immunology, 12(10), 975–983.

Oliveira, L. H. S. (1994) Vírus da imunodeficiência humana. In: Oliveira LHS, Bazin AR, editors. Virologia Humana. Rio de Janeiro: Cultura Médica, p. 192.

Rathore, A., Chatterjee, A., Yamamoto, N., & Dhole, T.N. (2008). Absence of H186R polymorphism in exon 4 of the APOBEC3G gene among north indian Iindividuals. Genetic Testing, 12(3), 453-456.

Reddy, K., Ooms, M., Letko, M., Garrett, N., Simon, V., & Ndung'u, T. (2016). Functional characterization of Vif proteins from HIV-1 infected patients with different APOBEC3G haplotypes. AIDS, 30(11), 1723-1729.

Reddy, K., Winkler, C. A., Werner, L., Mlisana, K., Abdool Karim, S. S., Ndung'u, T.; & CAPRISA Acute Infection Study Team. (2010). APOBEC3G expression is dysregulated in primary HIV-1 infection and polymorphic variants influence CD4+ T-cell counts and plasma viral load. AIDS, 24(2), 195-204.

Rehermann, B. & Nascimbeni, M. (2005). Immunology of hepatitis B virus and hepatitis C virus infection. Nature Reviews. Immunology, 5(3), 15-29.

Rose, K. M., Marin, M., Kozak, S. L., & Kabat, D. (2004). Transcriptional regulation of APOBEC3G, a cytidine deaminase that hypermutates human immunodeficiencyvirus. J Biol Chem, 279 (40), 41744-41749.

Rösler, C., Köck, J., Kann, M., Malim, M. H., Blum, H. E., Baumert, T. F., von Weizsäcker, F. APOBEC-mediated interference with hepadnavirus production. Hepatology, 42(2), 301-309.

Sadeghpour, S., Khodaee, S., Rahnama, M., Rahimi, H., & Ebrahimi, D. (2021). Human APOBEC3 variations and viral infection. Viruses, 13(7), 1366.

Seto, W. K., Lo, Y. R., Pawlotsky, J. M., & Yuen, M. F. (2018). Chronic hepatitis B virus infection. Lancet, 392(10161), 2313-2324.

Shinohara, M., Io, K., Shindo, K., Matsui, M., Sakamoto, T., Tada, K., Kobayashi, M., Kadowaki, N., & Takaori-Kondo, A. (2012). APOBEC3B can impair genomic stability by inducing base substitutions in genomic DNA in human cells. Scientific Reports, 2, 806.

Singh, K. K., Wang, Y., Gray, K. P., Farhad, M., Brummel, S., Fenton, T., Trout, R., & Spector, S. A. (2013). Genetic variants in the host restriction factor APOBEC3G are associated with HIV-1-related disease progression and central nervous system impairment in children. Journal of Acquired Immune Deficiency Syndromes, 62(2), 197-203.

Siriwardena, S. U., Chen, K., & Bhagwat, A. S. (2016). Functions and Malfunctions of Mammalian DNA-Cytosine Deaminases. Chemical Reviews, 116(20): 12688-12710.

Soriano, V., Vispo, E., Labarga, P., Medrano, J., & Barreiro, P. (2010). Viral hepatitis and HIV co-infection. Antiviral Research, 85(1), 303-315.

Valcke, H. S., Bernard, N. F., Bruneau, J., Alary, M., Tsoukas, C. M., & Roger, M. (2006). APOBEC3G genetic variants and their association with risk of HIV infection in highly exposed Caucasians. AIDS, 20(15), 1984-1986.

Vieira, V. C. & Soares, M. A. (2013). The role of cytidine deaminases on innate immune responses against human viral infections. BioMed Research International, 2013, 683095.

Welzel, T. M., Miley, W. J., Parks, T. L., Goedert, J. J., Whitby, D., & Ortiz-Conde, B. A. (2006). Real-time PCR assay for detection and quantification of hepatitis B virus genotypes A to G. Journal of Clinical Microbiology, 44(9), 3325-3333.

WHO. HIV/AIDS. Genebra: World Health Organization. (2021a).

WHO. Hepatitis B. Genebra: World Health Organization (2021b).

WHO. Hepatitis C. Genebra: World Health Organization (2021c).



How to Cite

GOMES, J. do A.; MERINO, A. S.; LUNGE, V. R. .; SIMON, D. Analysis of polymorphism of the APOBEC3G gene in HIV positive patients. Research, Society and Development, [S. l.], v. 11, n. 2, p. e38111225815, 2022. DOI: 10.33448/rsd-v11i2.25815. Disponível em: Acesso em: 13 jul. 2024.



Health Sciences