APOBEC3H explained

DNA dC->dU-editing enzyme APOBEC-3H, also known as Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3H or APOBEC-related protein 10, is a protein that in humans is encoded by the APOBEC3H gene.^[1]

Function

This gene encodes a member of the apolipoprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC) family of proteins. The encoded protein is a cytidine deaminase that has antiretroviral activity by generating lethal hypermutations in viral genomes. Polymorphisms and alternative splicing in this gene influence its antiretroviral activity and are associated with increased resistance to human immunodeficiency virus type 1 infection in certain populations. There are only one to two members of this family of genes in nonprimate mammals but at least seven members in primates. APOBEC3H is an antiviral effector. In Old world monkeys APOBEC3H has efficient antiviral activity against primate lentiviruses and it is sensitive to inactivation by the simian immunodeficiency virus Vif protein, and is capable of hypermutating retroviral genomes. The typical human APOBEC3H gene is inherently poorly expressed in primate cells and is ineffective at inhibiting retroviral replication.^[2] Importantly, different people have different strengths and potencies of APOBEC3H. People with version of the gene for APOBEC3H which produce stable variations of the protein can successfully limit HIV-1's ability to replicate.^[3]

Further reading

• Dang Y, Siew LM, Wang X, Han Y, Lampen R, Zheng YH . Human cytidine deaminase APOBEC3H restricts HIV-1 replication . The Journal of Biological Chemistry . 283 . 17 . 11606–14 . April 2008 . 18299330 . 2430661 . 10.1074/jbc.M707586200 . free .
• Wang X, Abudu A, Son S, Dang Y, Venta PJ, Zheng YH . Analysis of human APOBEC3H haplotypes and anti-human immunodeficiency virus type 1 activity . Journal of Virology . 85 . 7 . 3142–52 . April 2011 . 21270145 . 3067873 . 10.1128/JVI.02049-10 .
• Wedekind JE, Dance GS, Sowden MP, Smith HC . Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family business . Trends in Genetics . 19 . 4 . 207–16 . April 2003 . 12683974 . 10.1016/S0168-9525(03)00054-4 .
• OhAinle M, Kerns JA, Malik HS, Emerman M . Adaptive evolution and antiviral activity of the conserved mammalian cytidine deaminase APOBEC3H . Journal of Virology . 80 . 8 . 3853–62 . April 2006 . 16571802 . 1440450 . 10.1128/JVI.80.8.3853-3862.2006 .
• Vartanian JP, Guétard D, Henry M, Wain-Hobson S . Evidence for editing of human papillomavirus DNA by APOBEC3 in benign and precancerous lesions . Science . 320 . 5873 . 230–3 . April 2008 . 18403710 . 10.1126/science.1153201 . 2008Sci...320..230V . 23886176 .
• Ooms M, Majdak S, Seibert CW, Harari A, Simon V . The localization of APOBEC3H variants in HIV-1 virions determines their antiviral activity . Journal of Virology . 84 . 16 . 7961–9 . August 2010 . 20519396 . 2916534 . 10.1128/JVI.00754-10 .
• Tan L, Sarkis PT, Wang T, Tian C, Yu XF . Sole copy of Z2-type human cytidine deaminase APOBEC3H has inhibitory activity against retrotransposons and HIV-1 . FASEB Journal . 23 . 1 . 279–87 . January 2009 . 18827027 . 2626612 . 10.1096/fj.07-088781 . free .
• Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I . 6 . A genome annotation-driven approach to cloning the human ORFeome . Genome Biology . 5 . 10 . R84 . 2004 . 15461802 . 545604 . 10.1186/gb-2004-5-10-r84 . free .
• Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA . 6 . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proceedings of the National Academy of Sciences of the United States of America . 99 . 26 . 16899–903 . December 2002 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . free .
• Harari A, Ooms M, Mulder LC, Simon V . Polymorphisms and splice variants influence the antiretroviral activity of human APOBEC3H . Journal of Virology . 83 . 1 . 295–303 . January 2009 . 18945781 . 2612324 . 10.1128/JVI.01665-08 .
• Zhen A, Wang T, Zhao K, Xiong Y, Yu XF . A single amino acid difference in human APOBEC3H variants determines HIV-1 Vif sensitivity . Journal of Virology . 84 . 4 . 1902–11 . February 2010 . 19939923 . 2812409 . 10.1128/JVI.01509-09 .
• OhAinle M, Kerns JA, Li MM, Malik HS, Emerman M . Antiretroelement activity of APOBEC3H was lost twice in recent human evolution . Cell Host & Microbe . 4 . 3 . 249–59 . September 2008 . 18779051 . 2608726 . 10.1016/j.chom.2008.07.005 .
• Köck J, Blum HE . Hypermutation of hepatitis B virus genomes by APOBEC3G, APOBEC3C and APOBEC3H . The Journal of General Virology . 89 . Pt 5 . 1184–1191 . May 2008 . 18420796 . 10.1099/vir.0.83507-0 . free .
• Li MM, Wu LI, Emerman M . The range of human APOBEC3H sensitivity to lentiviral Vif proteins . Journal of Virology . 84 . 1 . 88–95 . January 2010 . 19828612 . 2798431 . 10.1128/JVI.01344-09 .

Notes and References

1. Web site: Entrez Gene: apolipoprotein B mRNA editing enzyme.
2. OhAinle M, Kerns JA, Malik HS, Emerman M . Adaptive evolution and antiviral activity of the conserved mammalian cytidine deaminase APOBEC3H . Journal of Virology . 80 . 8 . 3853–62 . April 2006 . 16571802 . 1440450 . 10.1128/JVI.80.8.3853-3862.2006 .
3. Refsland EW, Hultquist JF, Luengas EM, Ikeda T, Shaban NM, Law EK, Brown WL, Reilly C, Emerman M, Harris RS . 6 . Natural polymorphisms in human APOBEC3H and HIV-1 Vif combine in primary T lymphocytes to affect viral G-to-A mutation levels and infectivity . PLOS Genetics . 10 . 11 . e1004761 . November 2014 . 25411794 . 4238949 . 10.1371/journal.pgen.1004761 . free .