The HHV-6 Research Community mourns the loss of Niza Frenkel, PhD

Niza Frenkel, PhD

1947 - 2019

Niza Frenkel, a world-renowned virologist, passed away in Tel Aviv, Israel, on May 30, 2019. Born in Israel, she completed her graduate studies at the University of Chicago (MSc. and PhD) and her post-doctoral fellowship at the Weizmann Institute of Science in Israel. She then joined the faculty of the University of Chicago (1974-88) where she became a tenured, full professor, and where she made pioneering scientific contributions to the understanding of human herpesviruses including the applications of reassociation kinetics to measure nucleic acid abundance, features of the origins of lytic replication, identification and characterization of the virion host shutoff mRNAse and the structure of defective viral genomes. Subsequently, she joined the NIH, as Chief of Viral Diseases, where she was the first to discover Human Herpesvirus 7 (HHV-7) and to identify the difference between HHV-6A and HHV-6B by DNA structure, epidemiology and disease association. In 1991, she returned to Israel and established a lab at Tel Aviv University where she held the S. Daniel Abraham Chair of Molecular Virology and Gene Therapy. There she also served as the Head of the S. Daniel Abraham Institute for Molecular Virology. Niza’s additional groundbreaking contributions included the recognition of the universal signals necessary for herpesvirus DNA packaging in the structural infectious virions, and the first derivation of HSV, HHV-6 and HHV-7 amplicon vectors, which are now employed in many centers for gene therapy. For this, the American Society of Gene Therapy awarded her the special medal referring to her as the “Mother of All HSV Amplicons.” 

Mid-career, Niza was afflicted with multiple sclerosis. With absolute determination, courage, and optimism she continued her active research without interruptions and did not let the debilitating disease stand in her way.  She was a committed scientist and a dedicated, loving, and inspiring mother of two daughters and grandmother of four grandsons.

Niza Frenkel will be remembered as a wonderful friend, mentor, and brilliant, groundbreaking scientist, and her legacy will continue to live on through the significant work of the many students whom she mentored and impacted throughout her distinguished career.

Degrees:
1970 - M.Sc., Biochemistry, The University of Chicago
1972 - Ph.D., Virology, The University of Chicago

Education:
1967-1968 - Department of Microbiology, Tel-Aviv University, Israel
1968-1969 - College, The University of Chicago
1969-1970 - MSc. Department of Biochemistry, The University of Chicago
1970-1972 - PhD. Department of Molecular Genetics and Cell Biology and the Committees on Virology, Genetics and Cell Research, The University of Chicago

Scientific contributions:

  • Discovery of the human herpesvirus 7 (HHV-7). The virus is one of 8 different herpesviruses that infect man. HHV-7 causes grave febrile convulsions in children and it is tested for in patients by medical laboratories worldwide. It is studied molecularly by many virologists.
  • Recognition of the universal signals necessary for herpesvirus DNA packaging in the structural virions.
  • Derivation of the HSV-1, HHV-6 and HHV-7 amplicon vectors, employed in gene and cell therapy.
  • Identification and characterization of the virion host shutoff (vhs) mRNAse controlling both host and viral gene expression.
  • Cloning of HHV-6A into bacterial artifical chromosome (BAC).
  • Among the first to recognize that HHV-6A and HHV-6B are two distinct species

Prizes and awards:

  • 1973  The Mark Perry Galler Prize for the best Ph.D. dissertation, Biological Sciences, The University of Chicago, 1972-1973.
  • 1999 Commemoration of “the many contributions to the understanding of the biology and molecular biology of Human Herpes viruses 6 and 7. Presented May 14, 1999, at the 3rd International Conference of Human Herpes viruses 6 and 7. Clearwater Beach, Florida”.
  • 2001 Special recognition for the development of the herpesvirus amplicon, at the 4th Annual meeting of the American Society of  Gene Therapy. Seattle, WA.

Honors:

  • 2002 – 2017 S. Daniel Abraham Chair in Molecular Virology and Gene Therapy Tel Aviv University.
  • 2002 – 2017 The Director of the S. Daniel Abraham Institute of Molecular Virology, Tel Aviv University.
  • 2002 - 2013 Member of the board of the Israeli Society for Gene Therapy (ISGCT), Secretary of the ISGCT.
  • 2009 The Sarov prize from the Israel Society for Microbiology (ISM) in the annual meeting which was held in Bar-Ilan University. The prize is given to a scientist who had contributed a significant  contribution to the human microbial research in Israel and abroad, in basic and in clinical research.

Publications:

  1. Rozansky, R., Biano, S., Clejan, L., Frenkel, N., Bogokovsky, and Altmann, G. Penicillin b-lactamase and penicillin acylase formation by gram negative bacteria. Israel J. of Med. Sci. 5: 297-305, 1969.

  2. Frenkel, N., and Roizman, B. Herpes simplex virus: Genome size and redundancy studied by renaturation kinetics. J. Virology 8: 591-593, 1971.

  3. Moscona, M., Frenkel, N., and Moscona, A.A. Regulatory mechanisms in the induction of glutamine synthetase in the embryonic retina: Immuno-chemical studies. Dev. Biol. 28: 229-241, 1972.

  4. Frenkel, N., and Roizman, B. Ribonucleic acid synthesis in cells infected with herpes simplex virus: controls of transcription and of RNA abundance. Proc. Natl. Acad. Sci. USA 69: 2654-2658, 1972.

  5. Frenkel, N., and Roizman, B. Separation of the herpesvirus DNA duplex into unique fragments and intact strand on sedimentation in alkaline gradients. J. Virology 10: 565-572, 1972.

  6. Frenkel, N., Roizman, B., Cassai, E., and Nahmias, A. A DNA fragment of herpes simplex 2 and its transcription in human cervical cancer tissue. Proc. Natl. Acad. Sci. USA 69: 3784-3789, 1972.

  7. Roizman, B., and Frenkel, N. The transcription and state of herpes simplex virus DNA in a human cervical tumor: a comparison with productive infection of human cells. Proc. Fourth Lepetit Colloquium. North-Holland Publishing Co., pp. 202-217, 1973.

  8. Roizman, B., and Frenkel, N. The transcription and state of herpes simplex virus DNA in productive infection and in human cervical cancer tissue. Cancer Res. 33: 1402-1416, 1973.

  9. Frenkel, N., Silverstein, S., Cassai, E., and Roizman, B. RNA synthesis in cells infected with herpes simplex virus. VII. Control of transcription and of transcript abundancies of unique and common sequences of herpes simplex virus 1 and 2. J. Virology 11: 886-892, 1973.

  10. Silverstein, S., Bachenheimer, S.L., Frenkel, N., and Roizman, B. Relationship between post-transcriptional adenylation of herpes virus RNA and messenger RNA abundance. Proc. Natl. Acad. Sci. USA 70:2101-2104, 1973.

  11. Roizman, B., and Frenkel, N. Herpesvirus DNA: Structure, synthesis and transcription. In Molecular Studies in Viral Neoplasia. Proc. 25th Annual Symp. On Fundamental Cancer Res. of the M.D. Anderson Hospital and Tumor Inst. Williams and Wilkins Co., pp. 364-396, 1974.

  12. Frenkel, N., Lavi, S., and Winocour, E. The host DNA sequences in different populations of serially passaged SV40. J. Virology 60: 9-20, 1974.

  13. Frenkel, N., Rozenblatt, S., and Winocour, E. The repeated sequences in serially passaged SV40 DNA. In Tumor Virus Host Cell Interaction. A. Kolber, ed. Plenum Publishing Co., pp. 39-58, 1974.

  14. Winocour, E., Frenkel, N., Lavi, S., and Rozenblatt, S. SV40 DNA molecules which contain host cell DNA. Adv. in Exp. Med. and Biol. 44: 291-293, 1974.

  15. Winocour, E., Frenkel, N., Lavi, S., Osenholts, M., and Rozenblatt, S. Host substitution in SV40 and polyoma DNA. Cold Spring Harb. Symp. on Quant. Biol. 39: 101-108, 1975.

  16. Roizman, B., Hayward, G., Jacob, R., Wadsworth, S., Frenkel, N., Honess, R.W., and Kozak, M. Human herpesviruses I: A model for molecular organization and regulation of herpesviruses - A review. In Oncogenesis and Herpesviruses II. G. de The, M.A. Epstein, and H. zur Hausen, Eds. IARC, Lyon, pp. 3-38, 1975.

  17. Hayward, G.S., Frenkel, N., and Roizman, B. Anatomy of herpes simplex virus DNA: Strain differences and heterogeneity in the locations of restriction endonuclease cleavage sites. Proc. Natl. Acad. Sci. USA 72: 1768-1772, 1975.

  18. Frenkel, N., Jacob, R.J., Honess, R.W., Hayward, G.S., Locker, H., and Roizman, B. Anatomy of herpes simplex virus DNA. III. Characterization of defective DNA molecules and biological properties of virus populations containing them. J. Virology 16: 153-167, 1975.

  19. Roizman, B., and Frenkel, N. Does genital herpes cause cancer? - A midway assessment. In Sexually Transmitted Disease. R.D. Caterall, and C.S. Nicols, eds. Academic Press, New York, pp. 151-170, 1976.

  20. Frenkel N., Locker, H., Cox, B., Roizman, B., and Rapp, F. Herpes simplex virus DNA in transformed cells: Sequence complexity in five hamster cell lines and one derived hamster tumor. J. Virology 18: 885-893, 1976.

  21. Frenkel, N., Locker, H., Batterson, B., Hayward, G.S., and Roizman, B. Anatomy of herpes simplex virus DNA. VI. Defective DNA originates from the S component. J. Virology 20:527-531, 1976.

  22. Roizman, B., Frenkel, N., Kieff, E., and Spear, P. The structure and expression of human herpesvirus DNAs in productive infection and in transformed cells. In: Origins of Human Cancer. J.D. Watson and H. Hiatt, eds. Cold Spring Harbor, pp. 1069-1111, 1977.

  23. Frenkel, N., and Leiden, J. The presence and expression of herpes simplex virus DNA in transformed cells. In Integration and Excision of DNA molecules. 28th Mosbach Colloquium. P. Hofschneider and P. Starlinger, eds. Springer-Verlag, Berlin, pp. 71-77, 1978.

  24. Locker, H., and Frenkel, N. The DNA of serially passaged herpes simplex virus: Organization, origin, and homology to viral RNA. In Oncogenesis and Herpesviruses III. G. de The, W. Henle, and F. Rapp, eds. IARC, Lyon, pp. 75-85, 1978.

  25. Leiden, J.M., Frenkel, N., Polacek, D., and Rapp, F. Mapping of the herpes simplex virus DNA sequences in three herpes simplex virus Thymidine Kinase-transformed cell lines. In Oncogenesis and Herpesviruses III. G. de The, W. Henle, and F. Rapp, eds. IARC, Lyon, pp. 473-488, 1978.

  26. Locker, H., and Frenkel, N. Structure and origin of defective genomes contained in serially passaged herpes simplex virus type 1 (Justin). J. Virology 29: 1065-1077, 1979.

  27. Locker, H., and Frenkel, N. BamI, KpnI, and SalI restriction enzyme maps of the DNAs of herpes simplex virus strains Justin and F: Occurrence of heterogeneities in defined regions of the viral DNA. J. Virology 32: 429-441, 1979.

  28. Leiden, J.M., Frenkel, N., and Rapp, F. Identification of the herpes simplex virus DNA sequences present in six herpes simplex virus thymidine kinase-transformed mouse cell lines. J. Virology 33: 272-285, 1980.

  29. Frenkel, N., Locker, H., and Vlazny, D.A. Studies of defective herpes simplex viruses. Annals of the N.Y. Acad. Sci. 354: 347-370, 1980.

  30. Leiden, J.M., Frenkel, N., Sabourin, D., and Davidson, R.L. Mapping of the herpes simplex virus DNA sequences present in herpes simplex virustype-1 thymidine kinase-transformed cells. Somatic Cell Genetics 6: 789-798, 1980.

  31. Frenkel, N. Defective interfering herpesviruses. In The Human Herpesviruses. A.J. Nahmias, W.R. Dowdle, and R.S. Schinazy, eds. Elsevier-North Holland Inc., New York, pp. 91-120, 1981.

  32. Vlazny, D.A. and Frenkel, N. Replication of herpes simplex virus DNA: Localization of replication recognition signals within defective virus genomes. Proc. Natl. Acad Sci. USA 78: 742-746, 1981.

  33. Leiden, J.M., and Frenkel, N. Mapping of the HSV sequences in transformed cells. In Herpesvirus DNA: Recent Studies of the Viral Genome. Y. Becker, ed. Martinus Nijhoff Publishing, The Hague, pp. 197-221, 1981.

  34. Frenkel, N., Locker, H., and Vlazny, D. Structure and expression of class I and class II defective interfering HSV genomes. In Herpesvirus DNA: Recent Studies of the Viral Genome. Y. Becker, ed. Martinus Nijhoff Publishing, The Hague, pp. 149-184, 1981.

  35. Vlazny, D.A., Kwong, A.D., and Frenkel, N. Site-specific cleavage/packaging of herpes simplex virus DNA and the selective maturation of nucleocapsids containing full-length viral DNA. Proc. Natl. Acad. Sci. USA 79: 1423-1427, 1982.

  36. Frenkel, N., Spaete, R.R., Vlazny, D.A., Deiss, L.P., and Locker, H. The herpes simplex virus amplicon - a novel animal-virus cloning vector. In Eukaryotic Viral Vectors. Y. Gluzman, ed. Cold Spring Harbor Lab., pp. 205-209, 1982.

  37. Locker, J., Frenkel, N., and Halliburton, I. Structure and expression of class II defective herpes simplex virus genomes encoding infected cell polypeptide number 8. J. Virology 43: 574-593, 1982.

  38. Spaete, R.R., and Frenkel, N. The herpes simplex virus amplicon: A new eukaryotic defective-virus cloning-amplifying vector. Cell 30: 295-304, 1982.

  39. Read, G.S., and Frenkel, N. Herpes simplex virus mutants defective in the virion associated shut-off of host polypeptide synthesis and exhibiting abnormal synthesis of a (immediate early) viral polypeptides. J. Virology 46: 498-512, 1983.

  40. Frenkel, N., Deiss, L.P., Kwong, A.D., and Spaete, R.R. Defective virus vectors (amplicons) derived from herpes simplex viruses. In Gene Transfer and Cancer. M.L. Sternberg and M.L. Pearson, eds. Raven Press, pp. 105-113, 1984.

  41. Kwong, A.D., and Frenkel, N. The herpes simplex virus amplicon. II. Effect of size on the replication of constructed defective genomes containing eukaryotic DNA sequences. J. Virology 51: 595-603, 1984.

  42. Frenkel, N., Deiss, L.P., and Spaete, R.R. Studies of cis-acting replication functions of herpes simplex virus DNA. J. Cell. Biochem., Sup. 8B, 198, 1984.

  43. Frenkel, N., Deiss, L.P., and Spaete, R.R. Studies of HSV DNA propagation using HSV amplicons. In Herpesvirus. UCLA Symposia on Molecular and Cellular Biology, New Series, Volume 21. F. Rapp, ed. Alan R. Liss, Inc., New York, pp. 289-301, 1984.

  44. Spaete, R.R. and Frenkel, N. The herpes simplex virus amplicon. III. Analyses of cis replication functions. Proc. Natl. Acad. Sci. USA, 82: 694-698, 1985.

  45. Kwong, A.D., and Frenkel, N. The herpes simplex virus amplicon. V. Efficient expression of chicken ovalbumin from a chimeric gene introduced into constructed defective virus genomes. Virology 142: 421-425, 1985.

  46. Mocarski, E.S., Deiss, L.P., and Frenkel, N. The nucleotide sequence and structural features of a novel US Junction present in a defective herpes simplex virus genome. J. Virology 55:140-146, 1985.

  47. Deiss, L.P., and Frenkel, N. The herpes simplex virus amplicon: cleavage of concatmeric DNA is linked to packaging and involves the amplification of the terminally reiterated a sequence. J. Virology 57: 933-941, 1986.

  48. Manservigi, R., Cassai, E., Deiss, L.P., Di Luca, D., Valentina, S., and Frenkel, N. Herpes simplex virus and human papillomavirus DNA sequences in premalignant and malignant human genital tissues. Virology 155: 192-201, 1986.

  49. Meignier, B., Norrild, B., Thuning, C., Warren, J., Frenkel, N., Nahmias, A.J., Rapp, F., and Roizman, B. Cervical cancer was not induced in mice by long term frequent vaginal exposure to live or inactivated herpes simplex viruses. Int. J. Cancer 38: 387-394, 1986.

  50. Yehiely, F., Thuning, C., Meignier, B., Norrild, B., Warren, J., Nahmias, A.J., Rapp, F., Roizman, B. and Frenkel, N. Analyses of transplanted murine tumors for HSV DNA sequences. Int. J. Cancer 38: 395-403, 1986.

  51. Deiss, L.P., Chou, J., and Frenkel, N. Functional domains within the a sequence involved in the cleavage/packaging of herpes simplex virus DNA. J. Virology 59: 605-618, 1986.

  52. Kwong, A., and Frenkel, N. Herpes simplex virus infected cells contain function(s) which destabilize both host and viral mRNAs. Proc. Natl. Acad. Sci. USA. 84: 1926-1930, 1987.

  53. Strom, T., and Frenkel, N. Effects of herpes simplex virus on mRNA stability. J. Virol. 61: 2198-2207, 1987.

  54. Kwong, A. D., Kruper, J.A. and Frenkel, N. Herpes simplex virus virion host shutoff function. J. Virol 62: 912-921, 1988.

  55. Danovich, R.M. and N. Frenkel. Herpes simplex virus induces the replication of foreign DNA. Mol. Cell. Biol. 8: 3272-3281, 1988.

  56. Kwong A.D., and N. Frenkel. The herpes simplex virus virion host shutoff function. J. Virol. 63: 4834-4839, 1989.

  57. Di Luca, D., Katsafanas, G. Schirmer, E., Balachandran, N. and Frenkel,N. The replication of viral and cellular DNA in human herpesvirus 6 infected cells. Virology 175: 199-210, 1990.

  58. Roffman E., and Frenkel, N. Interleukin 2 inhibits the replication of HHV-6 in mature thymocytes. Virology 175: 591-594, 1990.

  59. Frenkel, N., E.C. Schirmer, Wyatt L,. S. Katsafanas G, Roffman, E., Danovich R.M. and June, C.H. Isolation of a new herpesvirus from human CD4+ T cells. Proc. Natl. Acad. Sci. USA. 87: 748-752, 1990.

  60. Frenkel, N., Schirmer, E.C., Katsafanas, G. and June C.H. T cell activation is required for efficient replication of human herpesvirus 6. J. Virol. 64: 4598-4602, 1990.

  61. Wyatt, L.S., Balachandran, N. and Frenkel N. Variations in the replication and antigenic properties of human herpesvirus 6 strains. J. Infect. Dis. 162: 852-857, 1990.

  62. Roffman, E., Albert, J.P., Goff, J.P., and Frenkel, N. A putative site for the acquisition of human herpesvirus 6 virion tegument. J. Virol., 64: 6308-6313, 1990.

  63. Frenkel, N., Roffman, E., Schirmer, E.C., Katsafanas, G., Wyatt, L.S. and June, C. Cellular and growth factor requirements for the replication of human herpesvirus 6 in primary lymphocyte cultures. In: Immunology and Prophylaxis of Human Herpesvirus Infections. eds. Lopez C., Mori, R., Roizman, B. and Whitley R.J. Plenum Publishing Corp. pp. 1-8,1990.

  64. Roffman, E., and Frenkel, N. Chemiluminescent quantitation of lymphocyte surface antigens. J. Immunological Methods. 138: 129-131, 1991.

  65. Schirmer, E.C., Wyatt, L.S., Yamanishi, K., Rodriguez, W., and Frenkel, N. Differentiation between two distinct classes of viruses now classified as human herpesvirus 6. Proc. Natl. Acad. Sci. USA. 88: 5922-5926, 1991.

  66. Wyatt, L.S., Rodriguez, W.J., Balachandran, N., and Frenkel, N. Human Herpesvirus 7: antigenic properties and prevalence in children and adults. J. Virol. 65: 6260-6265, 1991.

  67. Roffman, E., and N. Frenkel. Replication of human herpesvirus 6 in thymocytes activated by anti-CD3 antibodies. J. Inf. Dis. 164: 617-618, 1991.

  68. Frenkel, N., and Wyatt, L.S. Human herpesviruses 6 and 7 as exogenous agents in human lymphocytes. Develop. Biol. Standard. 76: 259-265, 1992.

  69. Wyatt, L. and Frenkel, N. Human herpesvirus 7 is a constitutive inhabitant of adult human saliva. J. Virol. 66: 3206-3209, 1992.

  70. Berneman, Z.N., Gallo, R.C., Ablashi, D.V., Frenkel, N., Katsafanas, G., Kramarsky, B. and Brus, I. Human herpesvirus 7 (HHV-7) strain JI: independent confirmation of HHV-7. J. Inf. Dis. 166: 690-691, 1992.

  71. Yoshikawa, T., Asano, Y., Kobayashi, I., Nakashima, T., Yazaki, T., Suga, S., Ozaki, T., Wyatt, L.S. and Frenkel, N. Seroepidemiology of human herpesvirus 7 in healthy children and adults in Japan. J. Med. Virol. 41: 319-323, 1993.

  72. Ablashi et al. Human herpesvirus-6 strain groups: a nomenclature. Arch. virol. 129: 363-366, 1993.

  73. Thompson, J., Choudhury, S., Kashanchi, F., Doniger, J., Berneman, Z., Frenkel, N. and Rosenthal, L.J. A transforming fragment within the direct repeat region of human herpesvirus type 6 that transactivates HIV-1. Oncogene 9: 1167-1175, 1994.

  74. Burns, J.C., Newburger, J.W., Sundello, R., Wyatt, L.S. and Frenkel, N. Seroprevalence of human herpesvirus 7 in patients with Kawasaki disease. Pediatr. Infect. Dis. 13: 168-169, 1994.

  75. Frenkel, N., Katsafanas, G.C., Wyatt, L.S., Yoshikawa, T. and Asano, Y. Bone marrow transplant recipients harbor the B variant of human herpesvirus 6 and develop high fever/rash disease. Bone Marrow Transplantation 14: 839-843, 1994.

  76. Frenkel, N., Singer, O. and Kwong, A.D. The herpes simplex virus amplicon - a versatile defective virus vector. Gene Therapy. 1: 540-546, 1994.

  77. Frenkel, N. and Rapaport, D. The human herpesvirus-6 (HHV-6) and HHV-7 PCR diagnosis. In: PCR Protocols for Diagnosis of Human and Animal Virus Diseases. Eds. Y. Becker and G. Darai, 243-251, 1995.

  78. Kwong, A. and Frenkel, N. Biology of herpes virus (HSV) defective viruses and development of the amplicon system. In Viral Vectors. Gene Therapy and Neuroscience Applications. Eds. Michael G. Kaplitt and Arthur D. Loewy. Academic Press, U.S.A. 25-42, 1995.

  79. Sever J.L., Rakusan, TA., Maadhava, E., Frenkel, N., Wyatt, L.S., Campos, J.M., O'Donnell, R.M. and Price, MV. Coinfection with herpesviruses in young children of HIV-1 infected women.  Pediatric AIDS and HIV infection: fetus to adolescent. 6: 75-82, 1995.

  80. Frenkel, N. and Roffman, E. Human herpesvirus 7. Virology. Third Edition. Eds. B.N. Fields, D. Knipe, P.M. Howley et al. Lippincott, Raven Press, pp. 2609-2633, 1996.

  81. Linquester, J.G., Inoue, N., Allen, R.D., Castelli, J.W., Stamey, F.R., Dambough, T.R., O’Brian, J.J., Danovich, R.M., Frenkel, N. and Pellett, P.E. Human herpesvirus 6 Variant B Genome: Restriction Endonuclease Mapping, Cloning and Identification of Colinearity with Human Cytomegalovirus and Human Herpesvirus 6 Variant A Genomes. Arch. Virol. 111: 367-379, 1996.

  82. Katsafanas, G.C., Schirmer, E.C., Wyatt, L.S. and Frenkel, N. In vitro activation of human herpesviruses 6 and 7 from latency. Proc. Natl. Acad. Sci. 93: 9788-9792, 1996.

  83. Frenkel, N. and Sarid, R. Herpes simplex virus amplicons. In: Gene Transfer Into Neurons Towards Gene Therapy of Neurological Disorders. Eds. Pedro Loewenstein and Lynn W. Enquist. John Wiley and Sons, England, pp. 143-148, 1996.

  84. Singer, O. and Frenkel, N. Human herpesvirus 7 (HHV-7) DNA: analyses of clones spanning the entire genome. Arch. Virol. 142: 287-303, 1997.

  85. Frenkel, N. and Sarid, R. HSV amplicons in gene therapy. In: Herpes Simplex    Virus - Protocols. The Humana Press/Wiley Series. “Methods in Molecular Medicine”, Totowa, NJ, USA. Eds. S. Moira Brown and Alasdair MacLean. pp. 227-235, 1997.

  86. Megaw, A.G., Rapaport, D,. Avidor, B., Frenkel, N., and Davison, A.J. The DNA sequence of the RK strain of human herpesvirus 7. Virology 244: 119-132, 1998.

  87. Romi, H., Singer, O., Rapaport, D., and Frenkel, N. Tamplicon 7, a novel T lymphotropic vector derived from human herpesvirus 7. J. Virol. 73: 7001-7007, 1999.

  88. Rapaport D., Engelhard D, Tagger G. Or R and Frenkel N. Antiviral prophylaxis may prevent human herpesvirus-6 reactivation in bone marrow transplant recipients. Transpl  Infect. Dis. 4(1): 6-10, 2002

  89. Borenstein R , Singer O , Moseri A , Frenkel N . Use of amplicon-6 vectors derived from human herpesvirus 6 for efficient expression of membrane-associated and -secreted proteins in T cells Virol.78 (9): 4730-43, 2004.

  90. Barzilai A, Zivoni-Elbom I, Sarid R, Noha E. and Frenkel N. The herpes simplex virus type 1 vhs-Ul41 gene secures viral replication by temporarily evading apoptotic cellular response to infection:  Vhs-Ul41 activity might require interactions with elements of cellular mRNA degradation machinery.  Virol.: 80(1): 505-513, 2006.

  91. Frenkel N. The History of the HSV amplicon: From Naturally Occurring Defective Genomes to Engineered Amplicon Vectors.  Current Gene Ther. 6(3): 277-301, 2006.

  92. Frenkel N, Borenstein R. Characterization of the Lyphotropic Amplicon-6 and Tamplicon-7 Vectors Derived from HHV-6 and HHV-7. Current Gene Ther. 6(3): 399-420, 2006.

  93. Mlechkovich G. and Frenkel N. Human herpesvirus 6A (HHV-6A) and HHV-6B alter E2F1/Rb pathways and E2F1 localization and cause cell cycle arrest in infected T cells. J. Virol.  81: 13499-508,  2007.

  94. Borenstein R, Frenkel N. Cloning human herpes virus 6A genome into bacterial artificial chromosomes and study of DNA replication intermediates. Proc. Natl. Acad. Sci. USA 106: 19138–19143, 2009.

  95. Borenstein R, Zeigerman H, Frenkel N. The DR1 and DR6 first exon of Human Herpesvirus 6A (HHV-6A) are not required for virus replication in culture and are found deleted in virus stocks which replicate well in T cell lines. J. Virol. 84(6): 2648-2656, 2010.

  96. Niza Frenkel, Ronen Borenstein and Haim Zeigerman. Selected aspects of Herpesvirus DNA replication, cleavage/packaging and the development and use of viral amplicon vectors. Book: “From the Hallowed Halls of Herpesvirology”, John A. Blaho and Joel D. Baines Editors, World Scientific Publishing / Imperial  College Press, chapter 3 p59-91, 2012.

  97. Dharam Ablashi, Henri Agut, Roberto Alvarez-Lafuente,  Duncan A. Clark, Stephen Dewhurst, Dario DiLuca, Louis Flamand, Niza Frenkel, Robert Gallo, Ursula A. Gompels, Per Höllsberg, Steven Jacobson, Mario Luppi, Paolo Lusso, Mauro Malnati, Peter Medveczky, Yasuko Mori, Philip E. Pellett, Joshua C. Pritchett, Koichi Yamanishi and  Tetsushi Yoshikawa.  Classification of HHV-6A and HHV-6B as distinct viruses. Arch  Virol. Nov  2013.

  98. Sharon E, Volchek L, Frenkel N. Human Herpesvirus 6 (HHV-6) alters E2F1/Rb pathways and utilizes the E2F1 transcription factor to express viral genes. Proc Natl Acad Sci U S A 111(1):451-6,  2014.

  99. Frenkel N, Sharon E, Zeigerman H. Roseoloviruses manipulate host cell cycle. Curr Opin Virol. 2014 Dec;9:162-6.

  1. Sharon E, Frenkel N. Human Herpesvirus 6A Exhibits Restrictive Propagation with Limited Activation of the Protein Kinase R-eIF2α Stress Pathway. J Virol. 2017 Apr 13;91(9). pii: e02120-16.