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Cell cycle checkpoints and pathogenesis of HIV-1 infection: a brief overview

  • Kesava Rao V. Kurapati , Thangavel Samikkannu , Venkata Subba Rao Atluri and Madhavan P.N. Nair EMAIL logo
Published/Copyright: July 19, 2014
Journal of Basic and Clinical Physiology and Pharmacology
From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 26 Issue 1

Abstract

To understand HIV pathogenesis or development is no simple undertaking and neither is the cell cycle which is highly complex that requires the coordination of multiple events and machinery. It is interesting that these two processes are interrelated, intersect and interact as HIV-1 infection results in cell cycle arrest at the G2 phase which is accompanied by massive CD4+ T cell death. For its own benefit, in an impressive manner and with the overabundance of tactics, HIV maneuvers DNA damage responses and cell cycle check points for viral replication at different stages from infection, to latency and to pathogenesis. Although the cell cycle is the most critical aspect involved in both viral and cellular replication, in this review, our main focus is on recent developments, including our own observations in the field of cell cycle proteins, checkpoints and strategies utilized by the viruses to manipulate these pathways to promote their own replication and survival. We will also discuss the emerging concept of targeting the replication initiation machinery for HIV therapy.

Keywords: cell cycle; DNA repair; G2/M checkpoint; HIV; HIV/AIDS; pathogenesis
Corresponding author: Madhavan P.N. Nair, PhD, Institute of Neuroimmune Pharmacology, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University, Modesto A. Maidique Campus, 11200 S.W. 8th Street, Miami, FL 33199, USA, Phone: +305 348 1493, Fax: +305 348 6021, E-mail:

Acknowledgments

We apologize to several authors whose primary research papers are not cited due to space constraints or inadvertent oversight.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research support played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Research funding: This study was supported by grants from the National Institutes Health (NIH): 1RO1MH085259, 1R01DA027049 and 1RO37DA025576 to Prof. Madhavan Nair.

Employment or leadership: None declared.

Honorarium: None declared.

References

1. Rogowska-Szadkowska D. Nobel Prize for medicine or physiology for discovery of HPV and HIV viruses – short history of discovery of HIV. HIV AIDS Rev 2008;7:5–9.Search in Google Scholar

2. Pincock S. HIV discoverers awarded Nobel Prize for medicine. Lancet 2008;372:1373.10.1016/S0140-6736(08)61571-8Search in Google Scholar

3. Barre-Sinoussi F. A significant discovery, now a dream for a cure. Bull World Health Organ 2009;87:10–11.10.2471/BLT.09.040109Search in Google Scholar

4. Gallo RC. The early years of HIV/AIDS. Science 2002;298:1728–9.10.1126/science.1078050Search in Google Scholar

5. Grossman Z, Meier-Schellersheim M, Paul WE, Picker LJ. Pathogenesis of HIV infection: what the virus spares is as important as what it destroys. Nat Med 2006;12:289–95.10.1038/nm1380Search in Google Scholar

6. Nair MP, Samikkannu T. Differential regulation of neurotoxin in HIV clades: role of cocaine and methamphetamine. Curr HIV Res 2012;10:429–34.10.2174/157016212802138742Search in Google Scholar

7. Bociaga-Jasik M, Lickiewicz B, Kalinowska-Nowak A, Ciesla A, Mach T, Garlicki A. Neurocognitive disorders in HIV infected patients. HIV AIDS Rev 2010;9:33–36.10.1016/S1730-1270(10)60066-5Search in Google Scholar

8. Knysz B, Szetela B, Gładysz A. Pathogenesis of HIV-1 infection – chosen aspects. HIV AIDS Rev 2007;6:7–11.10.1016/S1730-1270(10)60035-5Search in Google Scholar

9. Samikkannu T, Rao KV, Gandhi N, Saxena SK, Nair MP. Human immunodeficiency virus type 1 clade B and C Tat differentially induce indoleamine 2,3-dioxygenase and serotonin in immature dendritic cells: implications for neuroAIDS. J Neurovirol 2010;16:255–63.10.3109/13550284.2010.497809Search in Google Scholar PubMed

10. Konig R, Zhou Y, Elleder D, Diamond TL, Bonamy GM, Irelan JT, et al. Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replication. Cell 2008;135:49–60.10.1016/j.cell.2008.07.032Search in Google Scholar PubMed PubMed Central

11. Saxena SK, Tiwari S, Nair MP. A global perspective on HIV/AIDS. Science 2012;337:798.10.1126/science.337.6096.798Search in Google Scholar PubMed

12. “UNAIDS report on the global AIDS epidemic 2010.U.Search in Google Scholar

13. Kumari G, Singh RK. Highly active antiretroviral therapy for treatment of HIV/AIDS patients: current status and future prospects and the Indian scenario. HIV AIDS Rev 2012;11:5–14.10.1016/j.hivar.2012.02.003Search in Google Scholar

14. Cohen J. HIV/AIDS in America. Science 2012;337:168–71.10.1126/science.337.6091.168Search in Google Scholar PubMed

15. Futterman D. HIV/AIDS: the next generation. Science 2012;337:799.10.1126/science.337.6096.799-aSearch in Google Scholar PubMed

16. UNAIDS (2011) World AIDS Day Report 2011, UNAIDS.Search in Google Scholar

17. Hemelaar J. The origin and diversity of the HIV-1 pandemic. Trends Mol Med 2012;18:182–92.10.1016/j.molmed.2011.12.001Search in Google Scholar PubMed

18. Rambaut A. Human immunodeficiency virus. Phylogeny and the origin of HIV-1. Nature 2001;410:1047–8.10.1038/35074179Search in Google Scholar PubMed

19. Hemelaar J. Global trends in molecular epidemiology of HIV-1 during 2000–2007. AIDS 2011;25:679–89.10.1097/QAD.0b013e328342ff93Search in Google Scholar PubMed PubMed Central

20. Reddy PV, Pilakka-Kanthikeel S, Saxena SK, Saiyed Z, Nair MP. Interactive effects of morphine on HIV infection: role in HIV-associated neurocognitive disorder. AIDS Res Treat 2012;95:1–10.10.1155/2012/953678Search in Google Scholar PubMed PubMed Central

21. Buonaguro L, Tornesello ML, Buonaguro FM. Human immunodeficiency virus type 1 subtype distribution in the worldwide epidemic: pathogenetic and therapeutic implications. J Virol 2007;81:10209–19.10.1128/JVI.00872-07Search in Google Scholar PubMed PubMed Central

22. de Oliveira T, Pillay D, Gifford RJ. The HIV-1 subtype C epidemic in South America is linked to the United Kingdom. PLoS One 2010;5:e9311.10.1371/journal.pone.0009311Search in Google Scholar PubMed PubMed Central

23. Gandhi N, Saiyed Z, Thangavel S, Rodriguez J, Rao KV, Nair MP. Differential effects of HIV type 1 clade B and clade C Tat protein on expression of pro-inflammatory and anti-inflammatory cytokines by primary monocytes. AIDS Res Hum Retrov 2009;7:691–9.10.1089/aid.2008.0299Search in Google Scholar PubMed PubMed Central

24. Resh MD. Intracellular trafficking of HIV-1Gag: how Gag interacts with cell membranes and makes viral particles. AIDS Rev 2005;7:84–91.Search in Google Scholar

25. An P, Bleiber G, Duggal P, Nelson G, May M, Mangeat B, et al. APOBEC3G genetic variants and their influence on the progression to AIDS. J Virol 2004;78:11070–6.10.1128/JVI.78.20.11070-11076.2004Search in Google Scholar PubMed PubMed Central

26. Lawn SD, Butera ST, Folks TM. Contribution of immune activation to the pathogenesis and transmission of human immunodeficiency virus type 1 infection. Clin Microbiol Rev 2001;14:753–77.10.1128/CMR.14.4.753-777.2001Search in Google Scholar PubMed PubMed Central

27. Broder S. The development of antiretroviral therapy and its impact on the global HIV-1/AIDS pandemic. Antivir Res 2010;85:1–18.10.1016/j.antiviral.2009.10.002Search in Google Scholar PubMed PubMed Central

28. Kitchen CM, Kitchen SG, Dublin JA, Gottieb MS. Initial virological and immunologic response to highly active antiretroviral therapy predicts long term clinical outcome. Clin Infect Dis 2001;33:466–72.10.1086/321900Search in Google Scholar PubMed

29. Valenti WM. HAART is a cost-effective and improves outcomes. AIDS Read 2001;11:260–2.Search in Google Scholar

30. Gandhi N, Saiyed ZM, Napuri J, Samikkannu T, Reddy PV, Agudelo M, et al. Interactive role of human immunodeficiency virus type 1 (HIV-1) clade-specific Tat protein and cocaine in blood-brain barrier dysfunction: implications for HIV-1-associated neurocognitive disorder. J Neurovirol 2010;16:294–305.10.3109/13550284.2010.499891Search in Google Scholar PubMed

31. Appay V, Almeida JR, Sauce D, Autran B, Papagno L. Accelerated immune senescence and HIV-1 infection. Exp Gerontol 2007;42:432–7.10.1016/j.exger.2006.12.003Search in Google Scholar PubMed

32. Benito JM, Lopez M, Soriano V. The role of CD8+ T cell response in HIV infection. AIDS Rev 2004;6:79–88.Search in Google Scholar

33. Balzarini J. Metabolism and mechanism of antiretroviral action of purines and pyrimidine derivatives. Pharm World Sci 1994;16:113–26.10.1007/BF01880662Search in Google Scholar PubMed

34. Petrovas C, Casazza JP, Brenchley JM, Price DA, Gostick E, Adams WC, et al. PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. Jap J Exp Med 2006;203:2281–92.10.1084/jem.20061496Search in Google Scholar PubMed PubMed Central

35. Mohri H, Perelson AS, Tung K, Ribeiro RM, Ramaratnam B, Markowitz M, et al. Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. Jap J Exp Med 2001;194:1277–87.10.1084/jem.194.9.1277Search in Google Scholar PubMed PubMed Central

36. Rodriguez B, Sethi AK, Cheruvu VK, Mackay W, Bosch RJ, Kitahata M, et al. Predictive value of plasma HIV RNA level on rate of CD4 T cell decline in untreated HIV infection. J Am Med Assoc 2006;296:1498–506.10.1001/jama.296.12.1498Search in Google Scholar PubMed

37. Clerici M, Balotta C, Salvaggio A, Riva C, Trabattoni D, Papagno L, et al. Human immunodeficiency virus (HIV) phenotype and interleukin-2/interleukin-10 ratio are associated markers of protection progression in HIV infection. Blood 1996;88:574–9.10.1182/blood.V88.2.574.bloodjournal882574Search in Google Scholar

38. Schader SM, Wainberg MA. Insights into HIV-1 pathogenesis through drug discovery: 30 years of basic research and concerns for the future. HIV AIDS Rev 2011;10:91–8.10.1016/j.hivar.2011.09.003Search in Google Scholar

39. Wayengera M. Targeting persistent HIV infection: where and how, if possible? HIV AIDS Rev 2011;10:1–8.10.1016/j.hivar.2011.01.002Search in Google Scholar

40. Hasse AT. Pathogenesis of lentivirus infections. Nature 1986;322:130–6.10.1038/322130a0Search in Google Scholar

41. Rogowska-Szadkowska D, Sławomir-Chlabicz S. Primary HIV infection. HIV AIDS Rev 2008;7:10–4.10.1016/S1730-1270(10)60003-3Search in Google Scholar

42. Ratner L. Measurement of human immunodeficiency virus load and its relation to disease progression. AIDS Res Hum Retrov 1989;5:115–9.10.1089/aid.1989.5.115Search in Google Scholar PubMed

43. Reddy PV, Gandhi N, Samikkannu T, Saiyed Z, Agudelo M, Yndart A, et al. HIV-1 gp120 induces antioxidant response element-mediated expression in primary astrocytes: role in HIV associated neurocognitive disorder. Neurochem Int 2012;61:807–14.10.1016/j.neuint.2011.06.011Search in Google Scholar PubMed PubMed Central

44. Hillerman MR. Comparative biology and pathogenesis of AIDS and Hepatitis B viruses: related but different. AIDS Res Hum Retrov 1994;10:1409–19.10.1089/aid.1994.10.1409Search in Google Scholar PubMed

45. Johnson MC. Mechanisms for Env glycoprotein acquisition by retroviruses. AIDS Res Hum Retrov 2011;27:239–47.10.1089/aid.2010.0350Search in Google Scholar

46. Pilakka-Kanthikeel S, Saiyed ZM, Napuri J, Nair MP. MicroRNA: implications in HIV, a brief overview. J Neurovirol 2011;17:416–23.10.1007/s13365-011-0046-1Search in Google Scholar PubMed PubMed Central

47. Ada GL, McElrath MJ. HIV type 1 vaccine-induced cytotoxic T cell responses: potential role in vaccine efficacy. AIDS Res Hum Retrov 1997;13:205–10.10.1089/aid.1997.13.205Search in Google Scholar PubMed

48. Rodrigo AG. Dynamics of syncytium-inducing and nonsyncytium-inducing type 1 Human immunodeficiency viruses during primary infection. AIDS Res Hum Retrov 1997;13:1447–51.10.1089/aid.1997.13.1447Search in Google Scholar PubMed

49. Myers G. HIV: between past and future. AIDS Res Hum Retrov 1994;10:1317–24.10.1089/aid.1994.10.1317Search in Google Scholar PubMed

50. Gallo RC. Concluding remarks: human and related viruses of leukemia, lymphoma, and immunodeficiency: biology, pathogenesis, treatment, and prevention. AIDS Res Hum Retrov 1990;6:3–6.10.1089/aid.1990.6.3Search in Google Scholar

51. Nair MP, Saiyed ZM. Effect of methamphetamine on expression of HIV co-receptors and CC-chemokines by dendritic cells. Life Sci 2011;88:987–94.10.1016/j.lfs.2010.09.019Search in Google Scholar PubMed PubMed Central

52. Rodrigo AG, Mullins JI. Human immunodeficiency virus type 1 molecular evolution and the measure of selection. AIDS Res Hum Retrov 1996;12:1681–5.10.1089/aid.1996.12.1681Search in Google Scholar PubMed

53. Mackewicz C, Levy JA. CD8+ cell anti-HIV activity: nonlytic suppression of virus replication. AIDS Res and Hum Retrov 1992;8:1039–50.10.1089/aid.1992.8.1039Search in Google Scholar PubMed

54. Samikkannu T, Saiyed ZM, Rao KV, Babu DK, Rodriguez JW, Papuashvili MN, et al. Differential regulation of indoleamine-2,3-dioxygenase (IDO) by HIV type 1 clade B and C Tat protein. AIDS Res Hum Retrov 2009;3:329–35.10.1089/aid.2008.0225Search in Google Scholar PubMed PubMed Central

55. Milman G, Sharma O. Mechanisms of HIV/SIV mucosal transmission. AIDS Res Hum Retrov 1994;10:1305–12.10.1089/aid.1994.10.1305Search in Google Scholar PubMed

56. Milman G, D’Souza MP. HIV-mediated defects in immune regulation. AIDS Res Hum Retrov 1994;10:421–30.10.1089/aid.1994.10.421Search in Google Scholar PubMed

57. Markert ML. Perspective: research highlights at the duke university center for AIDS research: immunoreconstitution in HIV Infection: the role of the thymus. AIDS Res Hum Retrov 1996;12:751–5.10.1089/aid.1996.12.751Search in Google Scholar

58. Smithgall MD, Wong JG, Linsley PS, Haffar OK. Co-stimulation of CD4+ T cells via CD28 modulates Human Immunodeficiency Virus type 1 infection and replication in vitro. AIDS Res Hum Retrov 1995;11:885–92.10.1089/aid.1995.11.885Search in Google Scholar

59. Esser U, Speck RF, Deen KC, Atchison RE, Sweet R, Goldsmith MA. Molecular function of the CD4 D1 domain in co-receptor-mediated entry by HIV type 1. AIDS Res Hum Retrov 2000;16:1845–54.10.1089/08892220050195801Search in Google Scholar

60. Samikkannu T, Agudelo M, Gandhi N, Reddy PV, Saiyed ZM, Nwankwo D, et al. Human immunodeficiency virus type 1 clade B and C gp120 differentially induce neurotoxin arachidonic acid in human astrocytes: implications for neuroAIDS. J Neurovirol 2011;17:230–8.10.1007/s13365-011-0026-5Search in Google Scholar

61. Miller RJ, Cairns JS, Bridges S, Sarver N. Human immunodeficiency virus and AIDS: insights from animal lentiviruses. J Virol 2000;74:7187–95.10.1128/JVI.74.16.7187-7195.2000Search in Google Scholar

62. Shankarappa R, Margolick JB, Gange SJ, Rodrigo AG, Upchurch D, Farzadegan H, et al. Consistent viral evolutionary changes associated with the progression of human immunodeficiency virus type 1 infection. J Virol 1999;73:10489–502.10.1128/JVI.73.12.10489-10502.1999Search in Google Scholar

63. Chaurushiya MS, Weitzman MD. Viral manipulation of DNA repair and cell cycle checkpoints. DNA Repair 2009;8:1166–76.10.1016/j.dnarep.2009.04.016Search in Google Scholar

64. Giacinti C, Giordano A. RB and cell cycle progression. Oncogene 2006;25:5220–7.10.1038/sj.onc.1209615Search in Google Scholar

65. Sundarrajan M, Fernandis AZ, Subrahmanyam G, Prabhudesai S, Krishnamurthy SC, Rao KV. Overexpression of G1/S cyclins and PCNA and their relationship to tyrosine phosphorylation and dephosphorylation during tumor promotion by metanil yellow and Malachite green. Toxicol Lett 2000;116:119–30.10.1016/S0378-4274(00)00216-2Search in Google Scholar

66. Berk AJ. Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus. Oncogene 2005;24:7673–85.10.1038/sj.onc.1209040Search in Google Scholar PubMed

67. Zhao RY, Elder RT. Viral infections and cell cycle G2/M regulation. Cell Res 2005;15:143–9.10.1038/sj.cr.7290279Search in Google Scholar

68. Williams GH, Stoeber K. The cell cycle and cancer. J Pathol 2012;226:352–64.10.1002/path.3022Search in Google Scholar

69. Parekh P, Rao KV. Overexpression of cyclin D1 is associated with elevated levels of MAP kinases, Akt and Pak1 during diethylnitrosamine-induced progressive liver carcinogenesis. Cell Biol Int 2007;31:35–43.10.1016/j.cellbi.2006.09.005Search in Google Scholar

70. Taylor WR, Stark GR. Regulation of the G2/M transition by p53. Oncogene 2001;20:1803–15.10.1038/sj.onc.1204252Search in Google Scholar

71. Frank CL, Tsai L. Alternative functions of core cell cycle regulators in neuronal migration, neuronal maturation, and synaptic plasticity. Neuron 2009;62:312–26.10.1016/j.neuron.2009.03.029Search in Google Scholar

72. Poehlmann A, Roessner A. Importance of DNA damage checkpoints in the pathogenesis of human cancers. Pathol Res Pract 2010;206:591–601.10.1016/j.prp.2010.06.006Search in Google Scholar

73. Pateras IS, Apostolopoulou K, Niforou K, Kotsinas A, Gorgoulis VG. p57KIP2: “Kip”ing the cell under control. Mol Cancer Res 2009;7:1902–19.10.1158/1541-7786.MCR-09-0317Search in Google Scholar

74. Sundarrajan M, Fernandis AZ, Subrahmanyam G, Prabhudesai S, Krishnamurthy SC, Rao KV. Enhanced sequential expression of G1/S cyclins during experimental hepatocarcinogenesis and tyrosine phosphorylation. J Environ Pathol Tox 2001;20:189–97.10.1615/JEnvironPatholToxicolOncol.v20.i3.30Search in Google Scholar

75. Suvorova II, Katolikova NV, Pospelov VA. New insights into cell cycle regulation and DNA damage response in embryonic stem cells. Int Rev Cell Mol Biol 2012;299:161–98.10.1016/B978-0-12-394310-1.00004-7Search in Google Scholar

76. Ravitz MJ, Wenner CE. Cyclin-dependent kinase regulation during G1 phase and cell cycle regulation by TGF-beta. Adv Cancer Res 1997;71:165–207.10.1016/S0065-230X(08)60099-8Search in Google Scholar

77. Reynisdóttir I, Polyak K, Iavarone A, Massagué J. Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-beta. Gene Dev 1995;9:1831–45.10.1101/gad.9.15.1831Search in Google Scholar PubMed

78. Parekh P, Motiwale L, Naik N, Rao KV. Downregulation of cyclin D1 is associated with decreased levels of p38 MAP kinases, Akt/PKB and Pak1 during chemopreventive effects of resveratrol in liver cancer cells. Exp Toxicol Pathol 2011;63:167–73.10.1016/j.etp.2009.11.005Search in Google Scholar PubMed

79. Avanzo JL, Mennecier G, Mesnil M, Hernandez-Blazquez FJ, Fukumasu H, da Silva TC, et al. Deletion of a single allele of Cx43 is associated with a reduction in the gap junctional intercellular communication and increased cell proliferation of mouse lung pneumocytes type II. Cell Proliferat 2007;40:411–21.10.1111/j.1365-2184.2007.00440.xSearch in Google Scholar PubMed PubMed Central

80. Branzei D, Foiani M. Regulation of DNA repair throughout the cell cycle. Nat Rev Mol Cell Biol 2008;9:297–308.10.1038/nrm2351Search in Google Scholar PubMed

81. Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 2004;73:39–85.10.1146/annurev.biochem.73.011303.073723Search in Google Scholar PubMed

82. Jirawatnotai S, Hu Y, Livingston DM, Sicinski P. Proteomic identification of a direct role for cyclin D1 in DNA damage repair. Cancer Res 2012;72:4289–93.10.1158/0008-5472.CAN-11-3549Search in Google Scholar PubMed PubMed Central

83. David M, Petit D, Bertoglio J. Cell cycle regulation of Rho signaling pathways. Cell Cycle 2012;11:3003–10.10.4161/cc.21088Search in Google Scholar PubMed PubMed Central

84. Rao KV, Mahudawala DM, Redkar AA. Abrogation of cell cycle checkpoint controls during malignant transformation of syrian hamster embryo cells is associated with decreased sensitivity to apoptosis. J Environ Pathol Tox 2001;20:177–88.10.1615/JEnvironPatholToxicolOncol.v20.i3.20Search in Google Scholar

85. Romanov VS, Pospelov VA, Pospelova TV. Cyclin-dependent kinase inhibitor p21(Waf1): contemporary view on its role in senescence and oncogenesis. Biochemistry-Moscow+ 2012;77:575–84.10.1134/S000629791206003XSearch in Google Scholar PubMed

86. Hindley C, Philpott A. Coordination of cell cycle and differentiation in the developing nervous system. Biochem J 2012;444:375–82.10.1042/BJ20112040Search in Google Scholar PubMed PubMed Central

87. Stone A, Sutherland RL, Musgrove EA. Inhibitors of cell cycle kinases: recent advances and future prospects as cancer therapeutics. Crit Rev Oncol Hematol 2012;17:175–98.10.1615/CritRevOncog.v17.i2.40Search in Google Scholar

88. Swanton C, Mann DJ, Fleckenstein B, Neipel F, Peters G, Jones N. Herpes viral cyclin/Cdk6 complexes evade inhibition by CDK inhibitor proteins. Nature 1997;390:184–7.10.1038/36606Search in Google Scholar PubMed

89. Li H, Baskaran R, Krisky DM, Bein K, Grandi P, Cohen JB, et al. Chk2 is required for HSV-1 ICP0-mediated G2/M arrest and enhancement of virus growth. Virology 2008;375:13–23.10.1016/j.virol.2008.01.038Search in Google Scholar PubMed PubMed Central

90. Zhao F, Hou NB, Yang XL, He X, Liu Y, Zhang YH, et al. Ataxia telangiectasia-mutated-Rad3-related DNA damage checkpoint signaling pathway triggered by Hepatitis B virus infection. World J Gastroentero 2008;14:6163–70.10.3748/wjg.14.6163Search in Google Scholar PubMed PubMed Central

91. Ashra H, Rao KV. Elevated phosphorylation of Chk1 and decreased phosphorylation of Chk2 are associated with abrogation of G2/M checkpoint control during transformation of Syrian hamster embryo (SHE) cells by Malachite green. Cancer Lett 2006;237:188–98.10.1016/j.canlet.2005.05.044Search in Google Scholar PubMed

92. Parker GA, Touitou R, Allday MJ. Epstein-Barr virus EBNA3C can disrupt multiple cell cycle checkpoints and induce nuclear division divorced from cytokinesis. Oncogene 2000;19:700–9.10.1038/sj.onc.1203327Search in Google Scholar PubMed

93. Ohtani K, Iwanaga R, Arai M, Huang Y, Matsumura Y, Nakamura M. Cell type specific E2F activation and cell cycle progression induced by the oncogene product Tax of human T cell leukemia virus type 1. J Biol Chem 2000;275:11154–63.10.1074/jbc.275.15.11154Search in Google Scholar PubMed

94. Park HU, Jeong JH, Chung JH, Brady JN. Human T cell leukemia virus type 1 Tax interacts with Chk1 and attenuates DNA-damage induced G2 arrest mediated by Chk1. Oncogene 2004;23:4966–74.10.1038/sj.onc.1207644Search in Google Scholar PubMed

95. Sundarrajan M, Gupta S, Rao KV. Overexpression of cyclin D1 is associated with the decondensation of chromatin during den-induced sequential hepatocarcinogenesis. Cell Biol Int 2002;26:699–706.10.1006/cbir.2002.0923Search in Google Scholar PubMed

96. Nguyen DX, Westbrook TF, McCance DJ. Human papillomavirus type 16 E7 maintains elevated levels of the cdc25A tyrosine phosphatase during deregulation of cell cycle arrest. J Virol 2002;76:619–32.10.1128/JVI.76.2.619-632.2002Search in Google Scholar

97. Davy C, Doorbar J. G2/M cell cycle arrest in the life cycle of viruses. Virology 2007;368:219–26.10.1016/j.virol.2007.05.043Search in Google Scholar PubMed PubMed Central

98. Yang J, Xu ZP, Huang Y, Hamrick HE, Duerksen-Hughes PJ, Yu YN. ATM and ATR: sensing DNA damage. World J Gastroentero 2004;10:155–60.10.3748/wjg.v10.i2.155Search in Google Scholar PubMed PubMed Central

99. Cimprich KA, Cortez D. ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol 2008;9:616–27.10.1038/nrm2450Search in Google Scholar PubMed PubMed Central

100. Thanasoula M, Escandell JM, Suwaki N, Tarsounas M. ATM/ATR checkpoint activation downregulates CDC25C to prevent mitotic entry with uncapped telomeres. Embo J 2012;31:3398–410.10.1038/emboj.2012.191Search in Google Scholar PubMed PubMed Central

101. Kudoh A, Fujita M, Zhang L, Shirata N, Daikoku T, Sugaya Y, et al. Epstein-Barr virus lytic replication elicits ATM checkpoint signal transduction while providing an S phase-like cellular environment. J Biol Chem 2005;280:8156–63.10.1074/jbc.M411405200Search in Google Scholar PubMed

102. Smith J, Tho LM, Xu N, Gillespie DA. The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Adv Cancer Res 2010;108:73–112.10.1016/B978-0-12-380888-2.00003-0Search in Google Scholar PubMed

103. Shirata N, Kudoh A, Daikoku T, Tatsumi Y, Fujita M, Kiyono T, et al. Activation of ataxia telangiectasia-mutated DNA damage checkpoint signal transduction elicited by herpes simplex virus infection. J Biol Chem 2005;280:30336–41.10.1074/jbc.M500976200Search in Google Scholar PubMed

104. Stokes MP, Rush J, Macneill J, Ren JM, Sprott K, Nardone J, et al. Profiling of UV-induced ATM/ATR signaling pathways. Proc Natl Acad Sci USA 2007;104:19855–60.10.1073/pnas.0707579104Search in Google Scholar PubMed PubMed Central

105. Luo MH, Rosenke K, Czornak K, Fortunato EA. Human cytomegalovirus disrupts both ataxia telangiectasia mutated (ATM) protein and ATM-Rad3-related kinase-mediated DNA damage responses during lytic infection. J Virol 2007;81:1934–50.10.1128/JVI.01670-06Search in Google Scholar PubMed PubMed Central

106. Roshal M, Kim B, Zhu Y, Nghiem P, Planelles V. Activation of the ATR-mediated DNA damage response by the HIV-1 viral protein R. J Biol Chem 2003;278:25879–86.10.1074/jbc.M303948200Search in Google Scholar PubMed

107. Rao KV, Mahudawala DM, Redkar AA. Malignant transformation of Syrian hamster embryo (SHE) cells in primary culture by Malachite green: transformation is associated with abrogation of G2/M checkpoint control. Cell Biol Int 1998;22:581–9.10.1006/cbir.1998.0300Search in Google Scholar PubMed

108. Bose B, Motiwale L, Rao KV. DNA damage and G2/M arrest in Syrian hamster embryo cells during Malachite green exposure are associated with elevated phosphorylation of ERK1 and JNK1. Cancer Lett 2005;230:260–70.10.1016/j.canlet.2005.01.001Search in Google Scholar PubMed

109. Bose B, Gour RR, Motiwale L, Gupta S, Rao KV. Hyperphosphorylation of extracellular regulated kinase 2 (ERK2) and inhibition of JNK2 phosphorylation are associated with increased Sphase during transformation of Syrian hamster embryo cells by Malachite green. Cell Biol Int 2004;28:875–83.10.1016/j.cellbi.2004.09.001Search in Google Scholar PubMed

110. Gupta S, Sundarrajan M, Rao KV. Tumor promotion by metanil yellow and Malachite green during rat hepatocarcinogenesis is associated with dysregulated expression of cell cycle regulatory proteins. Teratog Carcinog Mutagen 2003;1(Suppl):301–12.10.1002/tcm.10056Search in Google Scholar PubMed

111. Ariumi P, Turelli M, Masutani D. DNA damage sensors ATM, ATR, DNA-PKcs, and PARP-1 are dispensable for human immunodeficiency virus type 1 integration. J Virol 2005;79:2973–8.10.1128/JVI.79.5.2973-2978.2005Search in Google Scholar PubMed PubMed Central

112. Daniel R, Kao G, Taganov K, Greger JG, Favorova O, Merkel G, et al. Evidence that the retroviral DNA integration process triggers an ATR-dependent DNA damage response. Proc Natl Acad Sci USA 2003;100:4778–83.10.1073/pnas.0730887100Search in Google Scholar PubMed PubMed Central

113. Sakai K, Barnitz RA, Chaigne-Delalande B, Bidere N, Lenardo MJ. Human immunodeficiency virus type 1 Vif causes dysfunction of Cdk1 and CyclinB1: implications for cell cycle arrest. Virol J 2011;8:219–27.10.1186/1743-422X-8-219Search in Google Scholar PubMed PubMed Central

114. Wang J, Reuschel EL, Shackelford JM, Jeang L, Shivers DK, Diehl JA, et al. HIV-1 Vif promotes the G1 to S phase cell cycle transition. Blood 2011;117:1260–9.10.1182/blood-2010-06-289215Search in Google Scholar PubMed PubMed Central

115. Huard S, Elder RT, Liang D, Li G, Zhao RY. Human immunodeficiency virus type 1 Vpr induces cell cycle G2 arrest through Srk1/MK2-mediated phosphorylation of Cdc25. J Virol 2008;82:2904–17.10.1128/JVI.01098-07Search in Google Scholar PubMed PubMed Central

116. Zimmerman ES, Sherman MP, Blackett JL, Neidleman JA, Kreis C, Mundt P, et al. Human Immunodeficiency Virus type 1 Vpr induces DNA replication stress in vitro and in vivo. J Virol 2006;80:10407–18.10.1128/JVI.01212-06Search in Google Scholar PubMed PubMed Central

117. Tsukiyama-Kohara K, Tone S, Maruyama I, Inoue K, Katsume A, Nuriya H, et al. Activation of the CKI-CDK-Rb-E2F pathway in full genome Hepatitis C virus-expressing cells. J Biol Chem 2004;279:14531–41.10.1074/jbc.M312822200Search in Google Scholar PubMed

118. Nakai-Murakami C, Shimura M, Kinomoto M, Takizawa Y, Tokunaga T, Taguchi T, et al. HIV-1 Vpr induces ATM-dependent cellular signal with enhanced homologous recombination. Oncogene 2007;26:477–86.10.1038/sj.onc.1209831Search in Google Scholar PubMed

119. Shtrichman R, Sharf R, Barr H, Dobner T, Kleinberger T. Induction of apoptosis by adenovirus E4 or f4 protein is specific to transformed cells and requires an interaction with protein phosphatase 2A. Proc Natl Acad Sci USA 1996;96:10080–5.10.1073/pnas.96.18.10080Search in Google Scholar PubMed PubMed Central

120. Margolis SS, Perry JA, Forester CM, Nutt LK, Guo Y, Jardim MA, et al. Role for the PP2A/B56 delta phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis. Cell 2006;127:759–73.10.1016/j.cell.2006.10.035Search in Google Scholar PubMed PubMed Central

121. WHO Traditional Medicine Strategy 2002-2005, 2002:1–61.Search in Google Scholar

122. Hedimbi M, Chinsembu KC. Ethnomedicinal study of plants used to manage HIV/AIDS-related disease conditions in the Ohangwena region, Namibia. Int J Med Plant Res 2012; 1:4–11.Search in Google Scholar

123. Homsy J, King R, Tenywa J, Kyeyune P, Opio A, Balaba D. Defining minimum standards of practice for incorporating African traditional medicine into HIV/AIDS prevention, care and support: a regional initiative in Eastern and Southern Africa. J Altern Complemt Med 2004;10:905–10.10.1089/1075553042476731Search in Google Scholar

Received: 2014-2-21
Accepted: 2014-5-17
Published Online: 2014-7-19
Published in Print: 2015-1-1

©2015 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Cell cycle checkpoints and pathogenesis of HIV-1 infection: a brief overview
  4. Behavior/Neuroprotection
  5. Neuroprotective effect of N-acetyl cysteine against streptozotocin-induced memory dysfunction and oxidative damage in rats
  6. Effect of (4a) a novel 5-HT3 receptor antagonist on chronic unpredictable mild stress induced depressive-like behavior in mice: an approach using behavioral tests battery
  7. Involvement of opioidergic and serotonergic systems in the analgesic activity of Cissus quadrangularis L. stem extract in mice
  8. Multiparameter rodent chronic model for complex evaluation of alcoholism-mediated metabolic violations
  9. Reproduction
  10. The methanol-soluble fraction of Millettia macrophylla (Fabaceae) stem bark endowed with estrogenic properties has adverse effects on the male reproductive system of Wistar rats
  11. Cardiovascular Function
  12. Kolaviron, a biflavonoid fraction from Garcinia kola, protects against isoproterenol-induced injury by mitigating cardiac dysfunction and oxidative stress in rats
  13. A comparative study to evaluate the cardiovascular risk of selective and nonselective cyclooxygenase inhibitors (COX-Is) in arthritic patients
  14. Metabolism
  15. Increased levels of serum γ-glutamyltransferase and uric acid on metabolic, hepatic and kidney parameters in subjects at high altitudes
  16. Phytotherapy
  17. Anti-inflammatory and antinociceptive activities of the aqueous leaf extract of Phyllanthus amarus Schum (Euphorbiaceae) in some laboratory animals
  18. Gastroprotective activity of essential oils from turmeric and ginger
  19. Decreased metabolism of 13C-caffeine via hepatic CYP1A2 in marasmus and kwashiorkor based on breath test
https://doi.org/10.1515/jbcpp-2014-0018
Keywords for this article
cell cycle; DNA repair; G2/M checkpoint; HIV; HIV/AIDS; pathogenesis

Articles in the same Issue

  1. Frontmatter
  2. Review
  3. Cell cycle checkpoints and pathogenesis of HIV-1 infection: a brief overview
  4. Behavior/Neuroprotection
  5. Neuroprotective effect of N-acetyl cysteine against streptozotocin-induced memory dysfunction and oxidative damage in rats
  6. Effect of (4a) a novel 5-HT3 receptor antagonist on chronic unpredictable mild stress induced depressive-like behavior in mice: an approach using behavioral tests battery
  7. Involvement of opioidergic and serotonergic systems in the analgesic activity of Cissus quadrangularis L. stem extract in mice
  8. Multiparameter rodent chronic model for complex evaluation of alcoholism-mediated metabolic violations
  9. Reproduction
  10. The methanol-soluble fraction of Millettia macrophylla (Fabaceae) stem bark endowed with estrogenic properties has adverse effects on the male reproductive system of Wistar rats
  11. Cardiovascular Function
  12. Kolaviron, a biflavonoid fraction from Garcinia kola, protects against isoproterenol-induced injury by mitigating cardiac dysfunction and oxidative stress in rats
  13. A comparative study to evaluate the cardiovascular risk of selective and nonselective cyclooxygenase inhibitors (COX-Is) in arthritic patients
  14. Metabolism
  15. Increased levels of serum γ-glutamyltransferase and uric acid on metabolic, hepatic and kidney parameters in subjects at high altitudes
  16. Phytotherapy
  17. Anti-inflammatory and antinociceptive activities of the aqueous leaf extract of Phyllanthus amarus Schum (Euphorbiaceae) in some laboratory animals
  18. Gastroprotective activity of essential oils from turmeric and ginger
  19. Decreased metabolism of 13C-caffeine via hepatic CYP1A2 in marasmus and kwashiorkor based on breath test
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