Correlation of Apolipoprotein B mRNA-editing Enzyme, Catalytic Polypeptide- like 3G Genetic Variant rs8177832 with HIV-1 Predisposition in Pakistani Population

Author(s): Khurshid Iqbal*, Muhammad Imran, Shafi Ullah, Muhsin Jamal, Yasir Waheed

Journal Name: Current HIV Research

Volume 16 , Issue 4 , 2018

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: Human immunodeficiency virus (HIV) infection is a global health burden which ultimately results in acquired immune deficiency syndrome (AIDS). There are multiple host factors which are capable of limiting HIV-1 replication. One of the most important host factors which inhibit HIV-1 DNA synthesis is the apolipoprotein B mRNA-editing enzyme, catalytic polypeptide- like 3G (APOBEC3G). Any genetic variation of this important host factor may influence the host susceptibility to viral infection.

Objective: The aim of the current study was to evaluate any correlation of APOBEC3G genetic variation rs8177832 with HIV-1 infection.

Methods: The study involved 142 healthy control and 100 HIV-1 infected subjects. The genetic variation rs8177832 of all studied subjects was determined by allele-specific polymerase chain reaction (AS-PCR).

Results: The results showed that the distribution of rs8177832 genotypes AA, AG and GG in healthy subjects and HIV-1 subjects was; 42.253%, 42.957%, 14.788% and 66%, 27%, 7% respectively. Statistical analyses of data showed that there was a significant variation in rs8177832 genotype AA in healthy control and HIV-1 infected subjects (42.257% vs 66%; p-value<0.001).

Conclusion: Thus it was concluded that APOBEC3G rs8177832 AA genotype contributes in genetic predisposition to HIV-1 infection in Pakistani population.

Keywords: HIV, pathogenesis, SNPs, Correlation, APOBEC3G, DC-SIGN.

Barré-Sinoussi F, Chermann J-C, Rey F, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983; 220: 868-71.
Hemelaar J, Gouws E, Ghys PD, Osmanov S. Global trends in molecular epidemiology of HIV-1 during 2000-2007. AIDS 2011; 25: 679-89.
Murray CJ, Ortblad KF, Guinovart C, et al. Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the global burden of disease study 2013. Lancet 2014; 384: 1005-70.
Kharsany AB, Karim QA. HIV infection and AIDS in Sub-Saharan Africa: current status, challenges and opportunities. Open AIDS J 2016; 10: 34.
Imran M, Manzoor S, Saalim M, et al. HIV‐1 and hijacking of the host immune system: the current scenario. APMIS 2016; 124: 817-31.
Oberle CS, Joos B, Rusert P, et al. Tracing HIV-1 transmission: envelope traits of HIV-1 transmitter and recipient pairs. Retrovirology 2016; 13: 016-0299.
An P, Bleiber G, Duggal P, et al. APOBEC3G genetic variants and their influence on the progression to AIDS. J Virol 2004; 78: 11070-6.
An P, Penugonda S, Thorball CW, et al. Role of APOBEC3F gene variation in HIV-1 disease progression and pneumocystis pneumonia. PLoS Genet 2016; 12: e1005921.
Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 2002; 3: 991-8.
Van Kooyk Y, Appelmelk B, Geijtenbeek TB. A fatal attraction: Mycobacterium tuberculosis and HIV-1 target DC-SIGN to escape immune surveillance. Trends Mol Med 2003; 9: 153-9.
D Urbano V. De Crignis E, Re MC. Host restriction factors and Human immunodeficiency Virus (HIV-1): a dynamic interplay involving all phases of the viral life cycle. Curr HIV Res 2018; 16(3): 184-207.
Bataller R, North KE, Brenner DA. Genetic polymorphisms and the progression of liver fibrosis: a critical appraisal. Hepatology 2003; 37: 493-503.
Janssen R, Bont L, Siezen CL, et al. Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. J Infect Dis 2007; 196: 826-34.
Powell EE, Edwards‐Smith CJ, Hay JL, et al. Host genetic factors influence disease progression in chronic hepatitis C. Hepatology 2000; 31: 828-33.
Piacentini L, Biasin M, Fenizia C, Clerici M. Genetic correlates of protection against HIV infection: the ally within. J Intern Med 2009; 265: 110-24.
A Estrada-Aguirre J, G Cazarez-Salazar S, A Ochoa-Ramirez L, et al. Protective effect of CCR5 Delta-32 allele against HIV-1 in Mexican women. Curr HIV Res 2013; 11: 506-10.
Kenny-Walsh E. The natural history of hepatitis C virus infection. Clin Liver Dis 2001; 5: 969-77.
Dolo A, Modiano D, Maiga B, et al. Difference in susceptibility to malaria between two sympatric ethnic groups in Mali. Am J Trop Med Hyg 2005; 72: 243-8.
Perera FP. Molecular epidemiology: insights into cancer susceptibility, risk assessment, and prevention. J Natl Cancer Inst 1996; 88: 496-509.
Duggal NK, Emerman M. Evolutionary conflicts between viruses and restriction factors shape immunity. Nat Rev Immunol 2012; 12: 687-95.
Kagoné TS, Bisseye C, Méda N, Testa J, Pietra V, Kania D, et al. A variant of DC-SIGN gene promoter associated with resistance to HIV-1 in serodiscordant couples in Burkina Faso. Asian Pac J Trop Biomed 2014; 7: S93-6.
Harris RS, Liddament MT. Retroviral restriction by APOBEC proteins. Nat Rev Immunol 2004; 4: 868-77.
Merindol N, Berthoux L. Restriction factors in HIV-1 disease progression. Curr HIV Res 2015; 13: 448-61.
Imran M, Manzoor S, Saalim M, et al. HIV-1 and hijacking of the host immune system: the current scenario. APMIS 2016; 124: 817-31.
Ayinde D, Casartelli N, Schwartz O. Restricting HIV the SAMHD1 way: through nucleotide starvation. Nat Rev Microbiol 2012; 10: 675-80.
Vieira VC, Soares MA. The role of cytidine deaminases on innate immune responses against human viral infections. BioMed Res Int 2013; 2013(683095)
Yang B, Chen K, Zhang C, Huang S, Zhang H. Virion-associated uracil DNA glycosylase-2 and apurinic/apyrimidinic endonuclease are involved in the degradation of APOBEC3G-edited nascent HIV-1 DNA. J Biol Chem 2007; 282: 11667-75.
Anderson JL, Hope TJ. APOBEC3G restricts early HIV-1 replication in the cytoplasm of target cells. Virology 2008; 375: 1-12.
Bishop KN, Holmes RK, Malim MH. Antiviral potency of APOBEC proteins does not correlate with cytidine deamination. J Virol 2006; 80: 8450-8.
Bishop KN, Verma M, Kim E-Y, Wolinsky SM, Malim MH. APOBEC3G inhibits elongation of HIV-1 reverse transcripts. PLoS Pathog 2008; 4: e1000231.
Holmes RK, Koning FA, Bishop KN, Malim MH. APOBEC3F can inhibit the accumulation of hiv-1 reverse transcription products in the absence of hypermutation comparisons with APOBEC3G. J Biol Chem 2007; 282: 2587-95.
Iwatani Y, Chan DS, Wang F, et al. Deaminase-independent inhibition of HIV-1 reverse transcription by APOBEC3G. Nucleic Acids Res 2007; 35: 7096-108.
Newman EN, Holmes RK, Craig HM, et al. Antiviral function of APOBEC3G can be dissociated from cytidine deaminase activity. Curr Biol 2005; 15: 166-70.
Mbisa JL, Barr R, Thomas JA, et al. Human immunodeficiency virus type 1 cDNAs produced in the presence of APOBEC3G exhibit defects in plus-strand DNA transfer and integration. J Virol 2007; 81: 7099-110.
Gillick K, Pollpeter D, Phalora P, Kim E-Y, Wolinsky SM, Malim MH. Suppression of HIV-1 infection by APOBEC3 proteins in primary human CD4+ T cells is associated with inhibition of processive reverse transcription as well as excessive cytidine deamination. J Virol 2013; 87: 1508-17.
Guo F, Cen S, Niu M, Saadatmand J, Kleiman L. Inhibition of-primed reverse transcription by human APOBEC3G during human immunodeficiency virus type 1 replication. J Virol 2006; 80: 11710-22.
Li X-Y, Guo F, Zhang L, Kleiman L, Cen S. APOBEC3G inhibits DNA strand transfer during HIV-1 reverse transcription. J Biol Chem 2007; 282: 32065-74.
Wang X, Ao Z, Chen L, Kobinger G, Peng J, Yao X. The cellular antiviral protein APOBEC3G interacts with HIV-1 reverse transcriptase and inhibits its function during viral replication. . J Virol 2012; 86: 3777-86.
Luo K, Wang T, Liu B, et al. Cytidine deaminases APOBEC3G and APOBEC3F interact with human immunodeficiency virus type 1 integrase and inhibit proviral DNA formation. J Biol Chem 2007; 81: 7238-48.
Mbisa JL, Bu W, Pathak VK. APOBEC3F and APOBEC3G inhibit HIV-1 DNA integration by different mechanisms. J Virol 2010; 84: 5250-9.
Norman JM, Mashiba M, McNamara LA, et al. The antiviral factor APOBEC3G enhances the recognition of HIV-infected primary T cells by natural killer cells. Nat Immunol 2011; 12: 975-83.
Mariani R, Chen D, Schrofelbauer B, et al. Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell 2003; 114: 21-31.
Reddy K, Winkler C, Werner L, et al. APOBEC3G expression is dysregulated in primary HIV-1 infection and a polymorphic variant influences CD4+ T cell counts and plasma viral load. AIDS (London, England) 2010; 24: 195.
Suguna S, Nandal D, Kamble S, Bharatha A, Kunkulol R. Genomic DNA isolation from human whole blood samples by non enzymatic salting out method. Int J Pharm Pharm Sci 2014; 6: 198-9.
Dean M, Carrington M, Winkler C, et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 1996; 273: 1856-62.
Yan N, Chen ZJ. Intrinsic antiviral immunity. Nat Immunol 2012; 13: 214-22.
An P, Bleiber G, Duggal P, et al. APOBEC3G genetic variants and their influence on the progression to AIDS. J Virol 2004; 78: 11070-6.
Do H, Vasilescu A, Diop G, et al. Exhaustive genotyping of the CEM15 (APOBEC3G) gene and absence of association with AIDS progression in a French cohort. J Infect Dis 2005; 191: 159-63.
Compaore TR, Soubeiga ST, Ouattara AK, et al. APOBEC3G variants and protection against HIV-1 infection in Burkina Faso. PLoS One 2016; 11: e0146386.
Do H, Vasilescu A, Diop G, et al. Exhaustive genotyping of the CEM15 (APOBEC3G) gene and absence of association with AIDS progression in a French cohort. J Infect Dis 2005; 191: 159-63.
Ezzikouri S, Kitab B, Rebbani K, et al. Polymorphic APOBEC 3 modulates chronic hepatitis B in M oroccan population. J Viral Hepat 2013; 20: 678-86.
De Maio FA, Rocco CA, Aulicino PC, Bologna R, Mangano A, Sen L. Effect of HIV-1 Vif variability on progression to pediatric AIDS and its association with APOBEC3G and CUL5 polymorphisms. Infect Genet Evol 2011; 11: 1256-62.

open access plus

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2018
Published on: 14 January, 2019
Page: [297 - 301]
Pages: 5
DOI: 10.2174/1570162X16666181018155827

Article Metrics

PDF: 25