APOBEC3G Inhibits DNA Strand Transfer during HIV-1 Reverse Transcription

Human APOBEC3G (hA3G) has been identified as an anti-HIV-1 host factor. The presence of hA3G in HIV-1 strongly inhibits the ability of the virus to produce new viral DNA upon infection. In this report, we demonstrate that the reduction of late viral DNA synthesis is due to the inhibition by hA3G of the strand transfer steps that occur during reverse transcription. Analysis of viral cDNA intermediates in vivo reveals that hA3G causes an inhibition of the minus and plus strand transfers, without having a significant impact on DNA elongation. Using an in vitro system to measure minus strand transfer similarly shows a dose-dependent reduction of strand transfer by hA3G. This inhibition of strand transfer occurs independently the editing activity of hA3G and is correlated with its ability to prevent RNaseH degradation of the template RNA. Human APOBEC3G (hA3G) has been identified as an anti-HIV-1 host factor. The presence of hA3G in HIV-1 strongly inhibits the ability of the virus to produce new viral DNA upon infection. In this report, we demonstrate that the reduction of late viral DNA synthesis is due to the inhibition by hA3G of the strand transfer steps that occur during reverse transcription. Analysis of viral cDNA intermediates in vivo reveals that hA3G causes an inhibition of the minus and plus strand transfers, without having a significant impact on DNA elongation. Using an in vitro system to measure minus strand transfer similarly shows a dose-dependent reduction of strand transfer by hA3G. This inhibition of strand transfer occurs independently the editing activity of hA3G and is correlated with its ability to prevent RNaseH degradation of the template RNA. Human APOBEC3G (hA3G) 3The abbreviations used are: hA3G, human APOBEC3G; PBS, primer binding site; HIV-1, human immunodeficiency virus, type 1; HA, hemagglutinin; Vif, virion infectivity factor; nt, nucleotide(s); RT, reverse transcription; -sss, minus strand strong stop. has been identified as an anti-HIV-1 host factor (1Sheehy A.M. Kim N.C. Choi J.D. Malim M.H. Nature. 2002; 418: 646-650Crossref PubMed Scopus (1941) Google Scholar). hA3G belongs to an APOBEC superfamily containing at least 10 members, which share a cytidine deaminase motif (a conserved His-X-Glu and Cys-X-X-Cys zinc coordination motif) (2Jarmuz A. Kim A. Bayliss J. Gisbourne J. Dunham I. Scott J. Navaratnam N. Genomics. 2002; 79: 285-296Crossref PubMed Scopus (599) Google Scholar). The APOBEC family in humans includes APOBEC1 (hA1), APOBEC2 (hA2), APOBEC3A-H (hA3A-H), and activation-induced cytidine deaminase. The APOBEC proteins are capable of inhibiting the replication of a wide variety of retroviruses and non-retroviruses, suggesting that these proteins represent a novel component of innate immunity to viral infection (for review, see Refs. 3Cullen B.R. J. Virol. 2006; 80: 1067-1076Crossref PubMed Scopus (221) Google Scholar and 4Yu X.-F. Curr. Opin. HIV AIDS. 2006; 1: 187-193Crossref PubMed Google Scholar). The virus counters hA3G’s anti-viral activity with the viral protein Vif (virion infectivity factor), which binds to hA3G, and targets hA3G for proteasomal degradation (5Stopak K. Kim C. Yonemoto W. Greene W.C. Mol. Cell. 2003; 12: 591-601Abstract Full Text Full Text PDF PubMed Scopus (614) Google Scholar, 6Yu X. Kim Y. Liu B. Luo K. Kong W. Mao P. Yu X.F. Science. 2003; 302: 1056-1060Crossref PubMed Scopus (1015) Google Scholar). Vif is thus required for HIV-1 replication in cell types that constitutively express hA3G (termed “non-permissive” cells), such as primary T lymphocytes, macrophages, and T-cell lines such as H9. Vif is not required for viral replication in cells not expressing hA3G (“permissive” cells) such as SupT1, Jurkat, 293, HeLa, and CEM-SS lines (7Fisher A.G. Kim B. Ivanoff L. Chamberlain M. Petteway S. Ratner L. Gallo R.C. Wong-Staal F. Science. 1987; 237: 888-893Crossref PubMed Scopus (295) Google Scholar, 8Strebel K. Kim D. Clouse K. Cohen D. Folks T. Martin M.A. Nature. 1987; 328: 728-730Crossref PubMed Scopus (376) Google Scholar, 9Gabuzda D.H. Kim K. Langhoff E. Terwilliger E. Dorfman T. Haseltine W.A. Sodroski J. J. Virol. 1992; 66: 6489-6495Crossref PubMed Google Scholar). HIV-1-containing hA3G shows a reduced ability to produce new viral DNA upon infecting cells (10Goncalves J. Kim Y. Zack J. Gabuzda D. J. Virol. 1996; 70: 8701-8709Crossref PubMed Google Scholar, 11Li J. Kim M.J. Volsky D.J. J. Cell. Biochem. 2004; 92: 560-572Crossref PubMed Scopus (38) Google Scholar, 12Mangeat B. Kim P. Caron G. Friedli M. Perrin L. Trono D. Nature. 2003; 424: 99-103Crossref PubMed Scopus (1263) Google Scholar, 13Mariani R. Kim D. Schrofelbauer B. Navarro F. Konig R. Bollman B. Munk C. Nymark-McMahon H. Landau N.R. Cell. 2003; 114: 21-31Abstract Full Text Full Text PDF PubMed Scopus (778) Google Scholar). It has been suggested that this results from the degradation of newly synthesized viral DNA, rather than the inhibition of new DNA synthesis. Thus, because the small amount of minus strand cDNA that is made in newly infected cells (∼5% of wild type) contains 1-2% of the cytosines deaminated by hA3G to form uracil (12Mangeat B. Kim P. Caron G. Friedli M. Perrin L. Trono D. Nature. 2003; 424: 99-103Crossref PubMed Scopus (1263) Google Scholar, 14Zhang H. Kim B. Pomerantz R.J. Zhang C. Arunachalam S.C. Gao L. Nature. 2003; 424: 94-98Crossref PubMed Scopus (925) Google Scholar, 15Harris R.S. Kim K.N. Sheehy A.M. Craig H.M. Petersen-Mahrt S.K. Watt I.N. Neuberger M.S. Malim M.H. Cell. 2003; 113: 803-809Abstract Full Text Full Text PDF PubMed Scopus (1156) Google Scholar, 16Lecossier D. Kim F. Clavel F. Hance A.J. Science. 2003; 300: 1112Crossref PubMed Scopus Google has been suggested that newly synthesized viral DNA in this by the DNA DNA such as a uracil DNA HIV-1 L. Kim S. M.A. J. R. M. J. Virol. PubMed Google Scholar, Kim F. I. Navarro Y. R. J. J. Virol. PubMed Google an and the by in a that is a for DNA in the degradation of the DNA Kim 2004; PubMed Scopus Google Scholar). a reduction in HIV-1 containing hA3G, an cells on the of hA3G, in the presence of hA3G, viral infectivity and synthesis of viral DNA are reduced with without viral Kim M. J. Virol. 2006; 80: PubMed Scopus Google Scholar). that hA3G Kim K. Yonemoto W. Greene W.C. Nature. PubMed Scopus Google Scholar, F. Kim S. M. J. L. J. Virol. 2006; 80: PubMed Scopus Google Scholar, Kim Craig H.M. Malim M.H. Sheehy A.M. Curr. Full Text Full Text PDF PubMed Scopus Google and Kim K.N. Malim M.H. J. Full Text Full Text PDF PubMed Scopus Google that cytidine deaminase activity strong anti-HIV-1 activity and a reduction in viral DNA and hA3G virus replication with editing C. Kim J. M. Malim M.H. F. PubMed Scopus Google Scholar, P. Kim B. S. S. Trono D. Science. 2004; PubMed Scopus Google Scholar). the that hA3G inhibits reverse transcription. that containing hA3G a reduction in the of viral DNA in newly infected cells and that this is correlated with a reduction in the of reverse F. Kim S. M. J. L. J. Virol. 2006; 80: PubMed Scopus Google Scholar). In this report, we that the reduction in late DNA synthesis for by the inhibition of minus and plus strand transfer steps in reverse transcription. and is a virus that contains HIV-1 The of as as and of hA3G has been S. Kim F. M. J. J. L. J. 2004; Full Text Full Text PDF PubMed Scopus (221) Google Scholar). The and of cells with these and the of from the cell as F. Kim S. M. J. L. J. Virol. 2006; 80: PubMed Scopus Google Scholar, S. Kim F. M. J. J. L. J. 2004; Full Text Full Text PDF PubMed Scopus (221) Google Scholar). cells with of HIV-1 DNA and of for of hA3G. The amount of DNA used for in by for hA3G with the with a for of and its infection with the HIV-1 from as F. Kim S. M. J. L. J. Virol. 2006; 80: PubMed Scopus Google Scholar). and viral proteins with The cell and viral by by with that are with HIV-1 hA3G and and with and of proteins by as (for hA3G, HA, and and (for from in the system of of HIV-1 the used to a the synthesis of viral cDNA intermediates in a cell SupT1, that been infected with HIV-1 containing hA3G. of of used to cells at for The cells with with and of cells containing to and at of cells and with and DNA the of DNA at an of used to viral cDNA intermediates containing for which minus strand strong DNA, minus strand transfer minus strand DNA, minus strand DNA, late minus strand DNA, and plus of and in with in The and of The of at of in the cells infected with of HIV-1, and at the of as with and as X. Kim A.M. S. A. 2006; PubMed Scopus Google Scholar). of containing of used to cDNA containing the of the viral reverse and the The amount of cDNA containing the of the viral with a of and as In Analysis of the an template of synthesized from the DNA X. Kim M. X. B. M. C. M.A. 2003; PubMed Scopus Google Scholar). The template the and and is to strand DNA to the PBS, used as primer in the The DNA and to the template by at for and to primer DNA, of of RT, and 10 of in a of of hA3G cell to the to on minus strand at for by the of of and at for by the by in a containing and the by strand transfer is by the of DNA, DNA strand strong DNA plus hA3G in the as a and by the and The HIV-1 used in this by synthesis as H. Kim D. B. Biochem. PubMed Scopus Google Scholar). HIV-1 as Kim B. G. J. Full Text PDF PubMed Google Scholar). protein a from of the of cell hA3G upon the minus strand transfer in the cells protein in the presence of which is hA3G of cDNA during in of DNA the minus strand transfer The DNA in the the with The as reverse The and In minus strand transfer used with a template by the of and an DNA primer in the presence of The at by of and the by HIV-1 a from M. Kim S. T. E. L. H. J. PubMed Scopus Google used as a HIV-1 of infectivity used the J. Kim S. H. M. L. J. Virol. 2002; PubMed Scopus Google Scholar, J. Kim M. J. Virol. 1992; 66: PubMed Google Scholar). of the of hA3G on DNA in infection of HIV-1-containing hA3G a strong reduction in viral DNA synthesis with HIV-1 not containing hA3G (10Goncalves J. Kim Y. Zack J. Gabuzda D. J. Virol. 1996; 70: 8701-8709Crossref PubMed Google Scholar, 11Li J. Kim M.J. Volsky D.J. J. Cell. Biochem. 2004; 92: 560-572Crossref PubMed Scopus (38) Google Scholar, 12Mangeat B. Kim P. Caron G. Friedli M. Perrin L. Trono D. Nature. 2003; 424: 99-103Crossref PubMed Scopus (1263) Google Scholar, 13Mariani R. Kim D. Schrofelbauer B. Navarro F. Konig R. Bollman B. Munk C. Nymark-McMahon H. Landau N.R. Cell. 2003; 114: 21-31Abstract Full Text Full Text PDF PubMed Scopus (778) Google Scholar). of the at which the viral DNA is of reduced of and late reverse in (10Goncalves J. Kim Y. Zack J. Gabuzda D. J. Virol. 1996; 70: 8701-8709Crossref PubMed Google Scholar, 13Mariani R. Kim D. Schrofelbauer B. Navarro F. Konig R. Bollman B. Munk C. Nymark-McMahon H. Landau N.R. Cell. 2003; 114: 21-31Abstract Full Text Full Text PDF PubMed Scopus (778) Google reduction of the J. Kim M.J. Volsky D.J. J. Cell. Biochem. 2004; 92: 560-572Crossref PubMed Scopus (38) Google Scholar). reduction in viral DNA with of this reduction due to a reduction in the synthesis of strong DNA due to the inhibition of F. Kim S. M. J. L. J. Virol. 2006; 80: PubMed Scopus Google Scholar). The of the reduction in late DNA is in this The of the HIV-1 DNA strand transfers, as in (for review, see C. Kim S. D. D. J. Biochem. 2004; PubMed Scopus Google Scholar). The synthesis of minus strand cDNA is from a to a in the of the viral as the primer binding of this DNA is by degradation of the template by which the DNA to the strand to the at the of the viral RNA. The synthesis of minus strand cDNA the and is by RNaseH degradation of the for a at the of This plus strand DNA which the of primer been a new is of the for the plus strand DNA to a strand by to in the minus strand and minus strand DNA synthesis are with the plus and minus of DNA as a template for of the In this we the reduction in the of late DNA synthesis is due to the inhibition by hA3G of DNA strand transfers, of these Using with of DNA, we a the synthesis of viral cDNA intermediates in a cell SupT1, that been infected with HIV-1 containing hA3G. in of used to viral cDNA intermediates containing for which DNA, strand transfer of and late minus strand DNA, and strand transfer late in DNA and late viral DNA the strand transfer at and with DNA at of the synthesis of DNA in the presence of hA3G, is in In with F. Kim S. M. J. L. J. Virol. 2006; 80: PubMed Scopus Google the presence of hA3G in HIV-1 a reduction in DNA and a reduction in the minus strand new is that the reduction in late DNA synthesis to inhibition of the DNA strand transfer steps and not the of DNA elongation. Thus, the in the minus strand viral DNA intermediates the strand transfer and for and that hA3G has significant impact on the of minus strand viral DNA the minus strand that an in DNA occurs the strand transfer results that the reduction in late viral DNA synthesis by hA3G by the inhibition of strand during reverse and this is an in vitro minus strand transfer hA3G the in ability of hA3G to minus strand transfer an in vitro that is and is in DNA with and to the PBS, to the of a template that in PBS, and and as the and in the strand transfer The of HIV-1 a DNA, the of HIV-1 is used to minus strand transfer and a transfer DNA of the by is in The synthesis of these DNA is in The in and strand transfer and has that of hA3G are from human cells H. Kim E. J. J.D. PubMed Scopus Google Scholar). This during reverse the of hA3G to HIV-1 is a from a of hA3G, we of hA3G, from to in the in which the of hA3G to the template of from P. Kim E. J. J.D. Liu J. K. H. S. A. 2003; PubMed Scopus Google to Kim I. Mol. 2004; PubMed Scopus Google Scholar). the in The in vitro strand transfer contains and thus an of in with of hA3G to the strand transfer the synthesis of is reduced and the of DNA and DNA from minus strand transfer with hA3G, are on a of minus strand transfer by hA3G from to as the hA3G from to in which hA3G with not in inhibition of minus strand transfer not hA3G binds to DNA and (2Jarmuz A. Kim A. Bayliss J. Gisbourne J. Dunham I. Scott J. Navaratnam N. Genomics. 2002; 79: 285-296Crossref PubMed Scopus (599) Google Scholar, Y. Kim H. K. J. Virol. 2006; 80: PubMed Scopus Google the of hA3G with D. Kim S. PubMed Scopus Google has upon strand that hA3G inhibits strand transfer by the of DNA to viral RNA. hA3G strongly reduced the not the DNA synthesis DNA and because the amount of DNA synthesis and This that the reduction in strand transfer DNA by hA3G not from a inhibition of reverse by hA3G. This is in in which of hA3G are in the of and in the synthesis of DNA are of of hA3G the hA3G inhibition of minus strand transfer upon the editing activity of this The editing activity of hA3G is for DNA Kim R. S. K. M. S. D. Landau N.R. Mol. 2004; PubMed Scopus Google and the DNA is a editing for hA3G during minus strand in minus strand transfer is by of in the DNA to the at the of viral RNA. to strand and the of DNA from the in vitro strand transfer for that been in the presence of hA3G, and to T This that DNA by hA3G least in the than of the Kim R. S. K. M. S. D. Landau N.R. Mol. 2004; PubMed Scopus Google Scholar). the ability of hA3G editing activity to minus strand transfer in by of the DNA synthesized the minus strand transfer in vivo to DNA, as The of hA3G are in hA3G and hA3G the zinc coordination hA3G contains the these that hA3G HIV-1, to viral DNA in vivo F. Kim S. M. J. L. J. Virol. 2006; 80: PubMed Scopus Google Scholar, S. Kim F. M. J. J. L. J. 2004; Full Text Full Text PDF PubMed Scopus (221) Google Scholar). cells with for of hA3G and of viral viral of these and hA3G cells infected with of containing of hA3G and the of form of hA3G on minus strand transfer The results are in hA3G and hA3G which editing the strand transfer in vivo as as hA3G. hA3G zinc coordination has on the strand results that the inhibition of strand transfer occur independently of the cytidine editing activity of hA3G. the of the and hA3G upon minus strand transfer in we to hA3G we the of of cells expressing of these to minus strand transfer in during the of cell This is not and not the strand transfer The in shows the of hA3G in the cell of in of cell of cell containing hA3G a reduction in in a dose-dependent of cell not expressing hA3G on minus strand transfer In the to the for strand transfer in the of hA3G are and that minus strand transfer from to and significant reduction in DNA synthesis results demonstrate as with hA3G, hA3G in cell used to minus strand transfer in and that in the cell this the of hA3G in cells on in vitro minus strand cells with for of hA3G, of cell that the of and hA3G are The of form of hA3G in the cell of on minus strand transfer and in The of inhibition of minus strand transfer in vivo is to that for the of hA3G in and the activity as hA3G. results that the inhibition of strand in vivo in occur independently of the cytidine editing activity of hA3G. of the of by the synthesis of DNA, the RNaseH activity with HIV the a required for of the DNA during minus strand transfer Kim J. I. K. Mol. 80: PubMed Scopus Google Scholar). in vivo and in the inhibition of minus strand transfer by hA3G is with a in the degradation of the template by cells with a containing and with the containing DNA for hA3G. Thus, types of in the presence of hA3G and in the presence of hA3G. the of viral in cells infected with of of the types of on of with primer used to reverse and the at the of viral which as of the template for the synthesis of DNA, and is by RNaseH to of DNA for the minus strand in at the amount of the in cells infected with containing hA3G reduced to of the at of the in the cells infected with hA3G. that hA3G the degradation of the template during reverse transcription. In we a of the of hA3G upon viral infectivity and from cells with of HIV-1 DNA and of hA3G expressing infectivity in the as The of used to and viral by in the of is that the inhibition of degradation by hA3G with its inhibition of viral the of hA3G on the degradation of template the in vitro minus strand transfer in that the template by the of and an DNA primer The by reverse in the of and hA3G, the with for by a reduction in The of of hA3G and by of in a dose-dependent in and of The of for reverse in significant reduction in the with without the of hA3G and that the in template from and that the of template by hA3G its ability to the degradation HIV-1 has been to the degradation of template during DNA strand transfer Kim M. R.J. J. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). an of hA3G with the of hA3G we such an for the inhibition of template by the in vitro in the of In we the amount of template during reverse with without in the presence of hA3G and this to a of the amount of strand transfer with hA3G from of the that reduced template degradation occurs independently of the presence of and is correlated with the of hA3G on the minus strand In this and F. Kim S. M. J. L. J. Virol. 2006; 80: PubMed Scopus Google we that a strong reduction in reverse an in the inhibition of HIV-1 replication by hA3G. that the reduction in of DNA is correlated with a reduction in the ability to reverse F. Kim S. M. J. L. J. Virol. 2006; 80: PubMed Scopus Google in this report, is that the reduction in late DNA synthesis is correlated with an inhibition of minus and plus strand in hA3G inhibits the minus and plus strand during reverse in In the presence of viral hA3G, DNA synthesis of viral DNA the minus strand transfer to without reduction in the synthesis of minus strand DNA and synthesis of plus strand DNA the plus strand transfer to that these in vivo represent inhibition of minus and plus strand we the ability of hA3G to minus strand transfer in In we that the inhibition of minus strand transfer by hA3G is upon the of hA3G. hA3G not synthesis of strong DNA, thus in vivo results that hA3G not DNA elongation. The that hA3G the of reverse is used as a primer F. Kim S. M. J. L. J. Virol. 2006; 80: PubMed Scopus Google not a DNA primer is by the that the to the viral template in vivo is by F. Kim S. M. J. L. J. Virol. 2006; 80: PubMed Scopus Google the DNA primer is in vitro that hA3G inhibits strand transfer during reverse as to late viral DNA results not a reduced viral DNA due to the degradation of newly synthesized In the reduction in late DNA in vitro in the presence of hA3G to degradation by of the DNA because are in the as in and of hA3G containing the zinc coordination strand transfer as as wild has that these and hA3G viral DNA in vivo at that of hA3G F. Kim S. M. J. L. J. Virol. 2006; 80: PubMed Scopus Google Scholar). This reduction in the of inhibition of viral DNA synthesis by these hA3G the of is with the that required for inhibition of viral DNA synthesis. the is not this a for editing activity of these It in the small amount of viral DNA that is synthesized in the cell in the presence of hA3G, the of is in of the that are reverse Kim R. S. K. M. S. D. Landau N.R. Mol. 2004; PubMed Scopus Google Scholar). is in the inhibition of synthesis of minus strand DNA that the for viral DNA reduction is not in the in viral DNA that is minus strand the of the DNA from the of template the degradation of template by the RNaseH activity with reverse that hA3G inhibits the degradation of the template in vivo and in The for this hA3G has been to to M. Kim S. M. G. R. E. Biochem. 2004; PubMed Scopus Google a hA3G and that RNaseH activity without DNA because the activity of HIV-1 is not to its RNaseH activity Kim J. Full Text PDF PubMed Google Scholar). because hA3G is to to DNA and Y. Kim H. K. J. Virol. 2006; 80: PubMed Scopus Google the of hA3G with the the to hA3G in reverse by binding to hA3G inhibits F. Kim S. M. J. L. J. Virol. 2006; 80: PubMed Scopus Google and DNA strand and are by Kim J. I. K. Mol. 80: PubMed Scopus Google in are required for the of hA3G HIV-1 S. Kim F. M. J. J. L. J. 2004; Full Text Full Text PDF PubMed Scopus (221) Google Scholar, Kim W. J. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar, M.A. Kim S. E. H. R. S. H. K. J. Virol. 79: PubMed Scopus Google Scholar, A. Kim B.R. 2004; 328: PubMed Scopus Google Scholar, Kim D. H. J. Virol. 2004; PubMed Scopus Google Scholar). is required for strand the in is not a strand transfer inhibition of of template by hA3G occurs independently of strand and of hA3G strand transfer by inhibiting template hA3G in to inhibiting strand transfer its with is to in strand transfer by of from the DNA template not in the in and of the DNA to the Kim J. I. K. Mol. 80: PubMed Scopus Google Scholar). hA3G has an on of these steps in strand transfer is not this a because has been that hA3G inhibits to viral its with F. Kim S. Y. R.J. L. J. Virol. PubMed Scopus Google Scholar). as in the of hA3G is to of minus strand transfer in vitro of template in HIV-1 from cells with of hA3G the viral of hA3G is than in from the cell F. Kim S. M. J. L. J. Virol. 2006; 80: PubMed Scopus Google Scholar). The as to the inhibition of strand transfer during viral DNA synthesis that occurs viral infection of cells is an of this of viral hA3G. that this is not upon on the of hA3G on of reverse F. Kim S. M. J. L. J. Virol. 2006; 80: PubMed Scopus Google Scholar). from cells a reduction of in of reverse upon infecting new from cells expressing hA3G a reduction in upon infection hA3G in the to this of Thus, the reduction of in that this in is not the of of hA3G. that cells expressing hA3G are not to cells such as which contains to the that the virus, and that the of hA3G. The of the of viral hA3G upon strand transfer in HIV-1 from cells such as cells is because of the of as a of and infection of HIV-1 DNA is made in the presence of hA3G, and that hA3G inhibits of this DNA K. Kim T. Liu B. C. J. Yu X.F. J. Virol. PubMed Scopus Google Scholar, Kim R. N. R.J. R.S. A. J. Virol. PubMed Scopus Google Scholar). Kim R. N. R.J. R.S. A. J. Virol. PubMed Scopus Google to plus strand hA3G with of to the of minus strand This results in of the of plus strand DNA, suggesting that this for the of that viral The ability of hA3G to is in with in which that hA3G inhibits template degradation to minus strand the Kim R. N. R.J. R.S. A. J. Virol. PubMed Scopus Google that hA3G plus strand transfer during HIV-1 reverse not an inhibition of minus strand transfer Kim R. N. R.J. R.S. A. J. Virol. PubMed Scopus Google Scholar). the that the in is than in system due to the of H. Kim E. J. J.D. PubMed Scopus Google Scholar). we in the this in a of that hA3G has upon reverse in cell types due to the of in the are the system and the we in this In report, cells with DNA for HIV-1, and DNA synthesis in cells infected with the HIV-1 from these In report, cells with an containing a viral expressing and and for and the proteins Vif, and with for and viral of the proteins by a virus containing that these The HIV-1 with virus and DNA synthesis by infecting cells with these Thus, in reverse in the cell type used the of viral the cell and the to of these the reverse that occurs upon HIV-1 the of hA3G on reverse is not It that these the DNA from minus and plus strand at viral DNA at with DNA from the minus and plus strand at and

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