The highly active antiretroviral treatment (HAART) has allowed people living with HIV to live longer with a better quality of life. However, toxicity and the emergence of drug resistance arise from HAART use. Therefore, new antiretroviral therapy is needed since no cure or vaccine is available against HIV. Virus-host interaction has been proven to be important in the last decade. Host factors such as the C-C chemokine receptor type 5 (CCR5), a receptor used by HIV to penetrate host cells, have led to the discovery of the Maraviroc, which is an antiretroviral medication used in the United States. In contrast, other factors like C-X-C Motif Chemokine Receptor 4 (CXCR4) and the Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3G (APOBEC3G), a potent host defense factor against HIV, is under investigation. APOBEC3G antiviral activity remains a possible therapeutic target against HIV. This systematic review aimed to synthesize the available evidence on the role of APOBEC3G polymorphisms and their expression on HIV infection disease progression in Africa. We used Web of Science, PubMed, Embase, and Google Scholar and searched for relevant publications in French or English reporting on APOBEC3G polymorphisms association with HIV infection in African populations from January 2009 to May 2023. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyzes) was used to process for reporting systematic review. Fifteen studies were included, of which seven were on APOBEC3G polymorphisms and eight were on APOBEC3G expression. Among the APOBEC3G polymorphisms, the most studied was H186R or rs8177832. The average of the minor allele frequency of H186R of APOBEC3G available for the studies included in this study was 0.29 with a 95% CI (0.172; 0.401) and varied from 0.108 reported in Uganda to 0.47 recorded from Burkina Faso. The polymorphism H186R was not associated with HIV status in Southern Africa. However, the referent allele of H186R was protective against HIV infection in Western Central Africa, while in West Africa, it was the minor allele (G) of H186R which was protective against HIV. This review warrants a need to increase research on APOBEC3G, from its variants to its hypermutations on the continent with an essential variety of HIV-1 subtypes, to impact the research on A3G-based anti-HIV strategies.
Taltynov, O., Desimmie, B.A., Demeulemeester, J., Christ, F. and Debyser, Z. (2012) Cellular Cofactors of Lentiviral Integrase: From Target Validation to Drug Discovery. Molecular Biology International, 2012, Article ID: 863405. https://doi.org/10.1155/2012/863405
MacArthur, R.D. and Novak, R.M. (2008) Reviews of Anti-Infective Agents: Maraviroc: The First of a New Class of Antiretroviral Agents. Clinical Infectious Diseases, 47, 236-241. https://doi.org/10.1086/589289
Weydert, C., De Rijck, J., Christ, F. and Debyser, Z. (2016) Targeting Virus-Host Interactions of HIV Replication. Current Topics in Medicinal Chemistry, 16, 1167-1190. https://doi.org/10.2174/1568026615666150901115106
Duggal, N.K. and Emerman, M. (2012) Evolutionary Conflicts between Viruses and Restriction Factors Shape Immunity. Nature Reviews Immunology, 12, 687-695. https://doi.org/10.1038/nri3295
Aarons, E., Fernandez, M., Rees, A., McClure, A., et al. (2007) Reciprocal Interactions between Human Immunodeficiency Virus and Hepatitis C Virus Infections. In: HIV and the Pathogenesis of AIDS, 3rd Edition, Cold Spring Harbor Laboratories, Stoneham, 688-689.
Jarmuz, A., Chester, A., Bayliss, J., Gisbourne, J., Dunham, I., Scott, J. and Navaratnam, N. (2002) An Anthropoid-Specific Locus of Orphan C to U RNA-Editing Enzymes on Chromosome 22. Genomics, 79, 285-296. https://doi.org/10.1006/geno.2002.6718
Hosseini, I. and Mac Gabhann, F. (2013) APOBEC3G-Augmented Stem Cell Therapy to Modulate HIV Replication: A Computational Study. PLOS ONE, 8, e63984. https://doi.org/10.1371/journal.pone.0063984
Harris, R.S. and Liddament, M.T. (2004) Retroviral Restriction by APOBEC Proteins. Nature Reviews Immunology, 4, 868-877. https://doi.org/10.1038/nri1489
Chiu, Y.L. and Greene, W.C. (2008) The APOBEC3 Cytidine Deaminases: An Innate Defensive Network Opposing Exogenous Retroviruses and Endogenous Retroelements. Annual Review of Immunology, 26, 317-353. https://doi.org/10.1146/annurev.immunol.26.021607.090350
Iyidogan, P. and Anderson, K.S. (2014) Current Perspectives on HIV-1 Antiretroviral Drug Resistance. Viruses, 6, 4095-4139. https://doi.org/10.3390/v6104095
Delviks-Frankenberry, K.A., Ackerman, D., Timberlake, N.D., Hamscher, M., Nikolaitchik, O.A., Hu, W.S., Torbett, B.E. and Pathak, V.K. (2019) Development of Lentiviral Vectors for HIV-1 Gene Therapy with Vif-Resistant APOBEC3G. Molecular Therapy—Nucleic Acids, 18, 1023-1038. https://doi.org/10.1016/j.omtn.2019.10.024
An, P. and Winkler, C.A. (2010) Host Genes Associated with HIV/AIDS: Advances in Gene Discovery. Trend in Genetics, 26, 119-131. https://doi.org/10.1016/j.tig.2010.01.002
Reddy, K., Winkler, C.A., Werner, L., Mlisana, K., Abdool Karim, S.S. and Ndung’u, T. (2010) APOBEC3G Expression Is Dysregulated in Primary HIV-1 Infection and Polymorphic Variants Influence CD4+ T-Cell Counts and Plasma Viral Load. Aids, 24, 195-204. https://doi.org/10.1097/QAD.0b013e3283353bba
Iwabu, Y., Kinomoto, M., Tatsumi, M., Fujita, H., Shimura, M., Tanaka, Y., Ishizaka, Y., Nolan, D., Mallal, S., Sata, T. and Tokunaga, K. (2010) Differential Anti-APOBEC3G Activity of HIV-1 Vif Proteins Derived from Different Subtypes. Journal of Biological Chemistry, 285, 35350-35358. https://doi.org/10.1074/jbc.M110.173286
Binka, M., Ooms, M., Steward, M. and Simon, V. (2012) The Activity Spectrum of Vif from Multiple HIV-1 Subtypes against APOBEC3G, APOBEC3F, and APOBEC3H. Journal of Virology, 86, 49-59. https://doi.org/10.1128/JVI.06082-11
Tishkoff, S.A., Reed, F.A., Friedlaender, F.R., Ehret, C., Ranciaro, A., Froment, A., et al. (2009) The Genetic Structure and History of Africans and African Americans. Science, 324, 1035-1044. https://doi.org/10.1126/science.1172257
Jakobsson, M., Scholz, S.W., Scheet, P., Gibbs, J.R., VanLiere, J.M., et al. (2008) Genotype, Haplotype and Copy-Number Variation in Worldwide Human Populations. Nature, 451, 998-1003. https://doi.org/10.1038/nature06742
Batzer, M.A. and Deininger, P.L. (2002) Alu Repeats and Human Genomic Diversity. Nature Reviews Genetics, 3, 370-379. https://doi.org/10.1038/nrg798
Rosenberg, N.A., Pritchard, J.K., Weber, J.L., Cann, H.M., Kidd, K.K., Zhivotovsky, L.A. and Feldman, M.W. (2002) Genetic Structure of Human Populations. Science, 298, 2381-2385. https://doi.org/10.1126/science.1078311
Li, J.Z., Absher, D.M., Tang, H., Southwick, A.M., Casto, A.M., Ramachandran, S., et al. (2008) Worldwide Human Relationships Inferred from Genome-Wide Patterns of Variation. Science, 319, 1100-1104. https://doi.org/10.1126/science.1153717
Genomes Project, C., Abecasis, G.R., Altshuler, D., Auton, A., Brooks, L.D., Durbin, R.M., Gibbs, R.A., Hurles, M.E. and McVean, G.A. (2010) A Map of Human Genome Variation from Population-Scale Sequencing. Nature, 467, 1061-1073. https://doi.org/10.1038/nature09534
Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G. and Group, P. (2009) Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. BMJ, 339, b2535. https://doi.org/10.1136/bmj.b2535
Aarsand, A.K., Roraas, T., Fernandez-Calle, P., Ricos, C., Diaz-Garzon, J., Jonker, N., Perich, C., Gonzalez-Lao, E., et al. (2018) The Biological Variation Data Critical Appraisal Checklist: A Standard for Evaluating Studies on Biological Variation. Clinical Chemistry, 64, 501-514. https://doi.org/10.1373/clinchem.2017.281808
Compaore, T.R., Soubeiga, S.T., Ouattara, A.K., Obiri-Yeboah, D., Tchelougou, D., Maiga, M., Assih, M., Bisseye, C., et al. (2016) APOBEC3G Variants and Protection against HIV-1 Infection in Burkina Faso. PLOS ONE, 11, e0146386. https://doi.org/10.1371/journal.pone.0146386
Compaore, T.R., Diarra, B., Assih, M., Obiri-Yeboah, D., Soubeiga, S.T., Ouattara, A.K., Tchelougou, D., et al. (2016) HBV/HIV Co-Infection and APOBEC3G Polymorphisms in a Population from Burkina Faso. BMC Infectious Diseases, 16, Article No. 336. https://doi.org/10.1186/s12879-016-1672-2
Lee, G.Q., Reddy, K., Einkauf, K.B., Gounder, K., Chevalier, J.M., Dong, K.L., et al. (2019) HIV-1 DNA Sequence Diversity and Evolution during Acute Subtype C Infection. Nature Communications, 10, Article No. 2737. https://doi.org/10.1038/s41467-019-10659-2
Land, A.M., Ball, T.B., Luo, M., Pilon, R., Sandstrom, P., Embree, J.E., et al. (2008) Human Immunodeficiency Virus (HIV) Type 1 Proviral Hypermutation Correlates with CD4 Count in HIV-Infected Women from Kenya. Journal of Virology, 82, 8172-8182. https://doi.org/10.1128/JVI.01115-08
Matume, N.D., Tebit, D.M., Gray, L.R., Turner, S.D., Rekosh, D., Bessong, P.O. and Hammarskjold, M.L. (2019) Characterization of APOBEC3 Variation in a Population of HIV-1 Infected Individuals in Northern South Africa. BMC Medical Genomics, 20, Article No. 21. https://doi.org/10.1186/s12881-018-0740-4
Mhandire, K., Duri, K., Mhandire, D., Musarurwa, C., Stray-Pedersen, B. and Dandara, C. (2016) Evaluating the Contribution of APOBEC3G Haplotypes, on Influencing HIV Infection in a Zimbabwean Pediatric Population. South African Medical Journal, 106, S119-S123. https://doi.org/10.7196/SAMJ.2016.v106i6.11013
Mous, K., Jennes, W., Camara, M., Seydi, M., Daneau, G., Mboup, S., Kestens, L. and Van Ostade, X. (2012) Expression Analysis of LEDGF/p75, APOBEC3G, TRIM5 Alpha, and Tetherin in a Senegalese Cohort of HIV-1-Exposed Seronegative Individuals. PLOS ONE, 7, e33934. https://doi.org/10.1371/journal.pone.0033934
Zhao, K., Ishida, Y., Oleksyk, T.K., Winkler, C.A. and Roca, A.L. (2012) Evidence for Selection at HIV Host Susceptibility Genes in a West Central African Human Population. BMC Evolutionary Biology, 12, Article No. 237. https://doi.org/10.1186/1471-2148-12-237
Kijak, G.H., Walsh, A.M., Koehler, R.N., Moqueet, N., et al. (2009) Genetic Complexity of TRIM5 and APOBEC in East Africa, in AIDS Vaccine 2009. Retrovirology, 6, P111. https://doi.org/10.1186/1742-4690-6-S3-P111
Ondoa, P., Gautam, R., Rusine, J., Lutter, R., Jurriaans, S., Kootstra, N., Karita, E. and van de Wijgert, J. (2015) Twelve-Month Antiretroviral Therapy Suppresses Plasma and Genital Viral Loads but Fails to Alter Genital Levels of Cytokines, in a Cohort of HIV-Infected Rwandan Women. PLOS ONE, 10, e0127201. https://doi.org/10.1371/journal.pone.0127201
Reddy, K., Ooms, M., Letko, M., Garrett, N., Simon, V. and Ndung’u, T. (2016) Functional Characterization of Vif Proteins from HIV-1 Infected Patients with Different APOBEC3G Haplotypes. Aids, 30, 1723-1729. https://doi.org/10.1097/QAD.0000000000001113
Ulenga, N.K., Sarr, A.D., Hamel, D., Sankale, J.L., Mboup, S. and Kanki, P.J. (2008) The Level of APOBEC3G (hA3G)-Related G-to-A Mutations Does Not Correlate with Viral Load in HIV Type 1-Infected Individuals. AIDS Research and Human Retroviruses, 24, 1285-1290. https://doi.org/10.1089/aid.2008.0072
WHO (2018) HIV/AIDS. https://www.who.int/news-room/fact-sheets/detail/hiv-aids
Skelton, M.M., Kampira, E.E., Wonkam, A.A., Mhandire, K.K., Kumwenda, J.J., Duri, K.K. and Dandara, C.C. (2014) Frequency Variation among Sub-Saharan Populations in Virus Restriction Gene, BST-2 Proximal Promoter Polymorphisms: Implications for HIV-1 Prevalence Differences among African Countries. OMICS, 18, 461-471. https://doi.org/10.1089/omi.2013.0127
Campbell, M.C. and Tishkoff, S.A. (2008) African Genetic Diversity: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping. Annual Review of Genomics and Human Genetics, 9, 403-433. https://doi.org/10.1146/annurev.genom.9.081307.164258
Quintana-Murci, L., Quach, H., Harmant, C., Luca, F., Massonnet, B., Patin, E., et al. (2008) Maternal Traces of Deep Common Ancestry and Asymmetric Gene Flow between Pygmy Hunter-Gatherers and Bantu-Speaking Farmers. Proceedings of the National Academy of Sciences of the United States of America, 105, 1596-1601. https://doi.org/10.1073/pnas.0711467105
Sadeghpour, S., Khodaee, S., Rahnama, M., Rahimi, H. and Ebrahimi, D. (2021) Human APOBEC3 Variations and Viral Infection. Viruses, 13, Article No. 1366. https://doi.org/10.3390/v13071366
Dalai, S.C., de Oliveira, T., Harkins, G.W., Kassaye, S.G., Lint, J., Manasa, J., Johnston, E. and Katzenstein, D. (2009) Evolution and Molecular Epidemiology of Subtype C HIV-1 in Zimbabwe. Aids, 23, 2523-2532. https://doi.org/10.1097/QAD.0b013e3283320ef3
Marechal, V., Jauvin, V., Selekon, B., Leal, J., Pelembi, P., Fikouma, V., et al. (2006) Increasing HIV Type 1 Polymorphic Diversity but No Resistance to Antiretroviral Drugs in Untreated Patients from Central African Republic: A 2005 Study. AIDS Research and Human Retroviruses, 22, 1036-1044. https://doi.org/10.1089/aid.2006.22.1036
Compaore, T.R., Soubeiga, S.T., Ouattara, A.K., Tchelougou, D., Bisseye, C., Bakouan, D.R., Compaore, I., et al. (2018) APOBEC3G Expression and HIV-1 Infection in Burkina Faso. Journal of Public Health in Africa, 9, Article No. 907. https://doi.org/10.4081/jphia.2018.907
Ulenga, N.K., Sarr, A.D., Thakore-Meloni, S., Sankale, J.L., Eisen, G. and Kanki, P.J. (2008) Relationship between Human Immunodeficiency Type 1 Infection and Expression of Human APOBEC3G and APOBEC3F. The Journal of Infectious Diseases, 198, 486-492. https://doi.org/10.1086/590212
Jin, X., Brooks, A., Chen, H., Bennett, R., Reichman, R. and Smith, H. (2005) APOBEC3G/CEM15 (hA3G) mRNA Levels Associate Inversely with Human Immunodeficiency Virus Viremia. Journal of Virology, 79, 11513-11516. https://doi.org/10.1128/JVI.79.17.11513-11516.2005
Khoja, S., Ojwang, P., Khan, S., Okinda, N., Harania, R. and Ali, S. (2008) Genetic Analysis of HIV-1 Subtypes in Nairobi, Kenya. PLOS ONE, 3, e3191. https://doi.org/10.1371/journal.pone.0003191
Guo, F., Cen, S., Niu, M., Saadatmand, J. and Kleiman, L. (2006) Inhibition of tRNA(3)(Lys)-Primed Reverse Transcription by Human APOBEC3G during Human Immunodeficiency Virus Type 1 Replication. Journal of Virology, 80, 11710-11722. https://doi.org/10.1128/JVI.01038-06
Mbisa, J.L., Barr, R., Thomas, J.A., Vandegraaff, N., Dorweiler, I.J., Svarovskaia, E.S., Brown, W.L., et al. (2007) Human Immunodeficiency Virus Type 1 cDNAs Produced in the Presence of APOBEC3G Exhibit Defects in Plus-Strand DNA Transfer and Integration. Journal of Virology, 81, 7099-7110. https://doi.org/10.1128/JVI.00272-07
Yu, N., Chen, F.C., Ota, S., Jorde, L.B., Pamilo, P., Patthy, L., et al. (2002) Larger Genetic Differences within Africans than between Africans and Eurasians. Genetics, 161, 269-274. https://doi.org/10.1093/genetics/161.1.269