Skip to main content
SpringerLink
Log in

Transgenic Models of Human Immunodeficiency Virus Type-1

  • Chapter
Transgenic Models of Human Viral and Immunological Disease

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 206))

Abstract

The use of transgenic technology has provided significant insights into the molecular pathogenesis of HIV-1 and its clinical manifestations. In particular, transgenic mice have suggested a potential role for Tat in Kaposi’s sarcoma, and a potential mechanism for the AIDS dementia complex. Furthermore, they have provided the strongest evidence that HIV-associated nephropathy is a direct consequence of viral infection rather than a complication of immune dysfunction or drug abuse. Transgenic mice have also shed light onto the molecular regulation of HIV-1 both at the transcriptional and posttranscriptional levels. In this chapter, we will review HIV-1 transgenic models, focusing on both single (Table 1) and multigenic (Table 2) murine lines that express viral genes and on transgenic mice expressing indicator genes under the control of the LTR.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  • Abramczuk JW, Pezen DS, Leonard JM, Monell Torrens E, Belcher JH, Martin MA, Notkins AL (1992) Transgenic mice carrying intact HIV provirus: biological effects and organization of a transgene. J Acquir Immune Defic Syndr 5: 196–203

    PubMed  CAS  Google Scholar 

  • Bruggeman LA, Thomson MM, Nelson PJ, Kopp JB, Rappaport J, Klotman PE, Klotman ME (1994) Patterns of HIV-1 mRNA expression in transgenic mice are tissue-dependent. Virology 202: 940–948

    Article  PubMed  CAS  Google Scholar 

  • Cavard C, Zider A, Vernet M, Bennoun M, Saragosti S, Grimber G, Briand P (1990) In vivo activation by ultraviolet rays of the human immunodeficiency virus type 1 long terminal repeat. J Clin Invest 86: 1369–1374

    Article  PubMed  CAS  Google Scholar 

  • Corallini A, Altavilla G, Pozzi L, Bignozzi F, Negrini M, Rimessi P, Gualandi F, Barbanti-Brodano G (1993) Systemic expression of HIV-1 tat gene in transgenic mice induces endothelial proliferation and tumors of different histotypes. Cancer Res53: 5569–5575

    PubMed  CAS  Google Scholar 

  • Corboy JR, Buzy JM, Zink MC, Clements JE (1992) Expression directed from HIV long terminal repeats in the central nervous system of transgenic mice. Science 258: 1804–1808

    Article  PubMed  CAS  Google Scholar 

  • Delli Bovi P, Donti E, Knowles DM, Friedman Kien A, Luciw PA, Dina D, Dalla Favera R, Basilico C (1986) Presence of chromosomal abnormalities and lack of AIDS retrovirus DNA sequences in AIDS-associated Kaposi’s sarcoma. Cancer Res46: 6333–6338

    Google Scholar 

  • Dickie P, Felser J, Eckhaus M, Bryant J, Silver J, Marinos N, Notkins AL (1991) HIV-associated nephropathy in transgenic mice expressing HIV-1 genes. Virology 185: 109–119

    Article  PubMed  CAS  Google Scholar 

  • Dickie P, Ramsdell F, Notkins AL, Venkatesan S (1993) Spontaneous and inducible epidermal hyperplasia in transgenic mice expressing HIV-1 Nef. Virology 197: 431–448

    Article  PubMed  CAS  Google Scholar 

  • Duvic M (1991) Papulosquamous disorders associated with human immunodeficiency virus infection. Dermatol Clin 9: 523–530

    Article  PubMed  CAS  Google Scholar 

  • Franks RF, Ray PE, Babbot CC, Bryant JL, Notkins AL, Santoro TJ, Klotman PE (1995) Maternal-fetal interactions affect growth of HIV-1 transgenic mice. Pediatr. Res. 37: 56–63

    Article  PubMed  CAS  Google Scholar 

  • Frucht DM, Lamperth L, Vicenzi E, Belcher JH, Martin MA (1991) Ultraviolet radiation increases HIV-long terminal repeat-directed expression in transgenic mice. AIDS Res. Hum. Retroviruses 7: 729–733

    Article  PubMed  CAS  Google Scholar 

  • Furth PA, Westphal H, Hennighausen L (1990) Expression from the HIV-LTR is stimulated by glucocorticoids and pregnancy. AIDS Res. Hum. Retroviruses 6: 533–560

    Article  Google Scholar 

  • Hammes SR, Dixon EP, Malim MH, Cullen BR, Greene WC (1989) Nef protein of human immunodeficiency virus type 1: evidence against its role as a transcriptional inhibitor. Proc Natl Acad Sci USA 86: 9549–9553

    Article  PubMed  CAS  Google Scholar 

  • Huang SK, Martin FJ, Jay G, Vogel J, Papahadjopoulos D, Friend DS (1993) Extravasation and transcytosis of liposomes in Kaposi’s sarcoma-like dermal lesions of transgenic mice bearing the HIV tat gene. AM J Pathol 143: 10–14

    PubMed  CAS  Google Scholar 

  • Huang YQ, Buchbinder A, Li JJ, Nicolaides A, Zhang WG, Friedman Kien AE (1992) The absence of Tat sequences in tissues of HIV-negative patients with epidermic Kaposi’s sarcoma AIDS 6: 1139–11

    CAS  Google Scholar 

  • Iwakura Y, Shioda T, Tosu M, Yoshida E, Hayashi M, Nagata T, Shibuta H (1992) The induction of cataracts by HIV-1 in transgenic mice. AIDS 6: 1069–1075

    Article  PubMed  CAS  Google Scholar 

  • Jolicoeur P, Laperriere A, Beaulieu N (1992) Efficient production of human immunodeficiency virus proteins in transgenic mice. J Virol 66: 3904–3908

    PubMed  CAS  Google Scholar 

  • Khillan JS, Deen KC, Yu SH, Sweet RW, Rosenberg M, Westphal H (1988) Gene transactivation mediated by the TAT gene of human immunodeficiency virus in transgenic mice. Nucleic Acids Res 16: 1423–1430

    Article  PubMed  CAS  Google Scholar 

  • Kopp JB, Klotman ME, Adler SH, Bruggeman LA, Eckhaus M, Dickie P, Marinos NJ, Bryant JL, Notkins AL, Klotman PE (1992) Progressive glomerulosclerosis and enhanced renal accumulation of basement membrane components in mice transgenic for HIV-1 genes. Proc Natl Acad Sci USA 89: 1577–1581

    Article  PubMed  CAS  Google Scholar 

  • Kopp JB, Rooney JF, Wohlenberg C, Dorfman N, Marinos NJ, Bryant JL, Katz SI, Notkins AL, Klotman PE (1993) Cutaneous disorders and viral gene expression in HIV-1 transgenic mice. AIDS Res Hum Retroviruses 9: 267–275

    Article  PubMed  CAS  Google Scholar 

  • Kopp JB, Ray PE, Adler SH, Bruggeman LA, Mangurian CV, Owens JW, Eckhaus MA, Bryant JL, Klotman PE (1994) Nephropathy in HIV-transgenic mice. In: Koide H, Hayashi T (eds) Extracellular matrix in the kidney; Karger, Basel, pp 194–204

    Google Scholar 

  • Leonard JM, Abramczuk JW, Pezen DS, Rutledge R, Belcher JH, Hakim F, Shearer G, Lamperth L, Travis W, Fredrickson T, Notkins AL, Martin MA (1988) Development of disease and virus recovery in transgenic mice containing HIV proviral DNA. Science 242: 1665–1670

    Article  PubMed  CAS  Google Scholar 

  • Leonard JM, Khillan JS, Gendelman HE, Adachi A, Lorenzo S, Westphal H, Martin MA, Meltzer MS (1989) The human immunodeficiency virus long terminal repeat is preferentially expressed in Langerhans cells in transgenic mice. AIDS Res Hum Retroviruses 5: 421–430

    Article  PubMed  CAS  Google Scholar 

  • Lindemann D, Wilhelm R, Renard P, Althage A, Zinkernagel R, Mous J (1994) Severe immunodeficiency associated with a human immunodeficiency virus 1 NEF/3’-long terminal repeat transgene. J Exp Med 179: 797–807

    Article  PubMed  CAS  Google Scholar 

  • Mehtali M, Munschy M, Ali Hadji D, Kieny MP (1992) A novel transgenic mouse model for the in vivo evaluation of anti-human immunodeficiency virus type 1 drugs. AIDS Res Hum Retroviruses 8: 1959–1965

    Article  PubMed  CAS  Google Scholar 

  • Morrey JD, Bourn SM, Bunch TD, Jackson MK, Sidwell RW, Barrows LR, Daynes RA, Rosen CA (1991) In vivo activation of human immunodeficiency virus type 1 long terminal repeat by UV type A (UV-A) light plus psoralen and UV-B light in the skin of transgenic mice. J Virol 65: 5045–5051

    PubMed  CAS  Google Scholar 

  • Morrey JD, Bourn SM, Bunch TD, Sidwell RW, Rosen CA (1992) HIV-1 LTR activation model: evaluation of various agents in skin of transgenic mice. J Acquir Immune Defic Syndr 5: 1195–1203

    PubMed  CAS  Google Scholar 

  • Morrey JD, Jackson MK, Bunch TD, Sidwell RW (1993) Activation of the human immunodeficiency virus type 1 long terminal repeat by skin-sensitizing chemicals in transgenic mice. Intervirology 36: 65–71

    PubMed  CAS  Google Scholar 

  • Pezen DS, Leonard JM, Abramczuk JW, Martin MA (1991) Transgenic mice carrying HIV proviral DNA. Biotechnology16: 213–226

    PubMed  CAS  Google Scholar 

  • Rao TK (1991a) Human immunodeficiency virus (HIV) associated nephropathy. Annu Rev Med 42: 391–401

    Article  PubMed  CAS  Google Scholar 

  • Rao TK (1991b) Clinical features of human immunodeficiency virus associated nephropathy. Kidney. lnt Suppl 35: S13–S18

    CAS  Google Scholar 

  • Rao TK, Filippone EJ, Nicastri AD, Landesman SH, Frank E, Chen CK, Friedman EA (1984) Associated focal and segmental glomerulosclerosis in the acquired immunodeficiency syndrome. N Engl J Med 310: 669–673

    Article  PubMed  CAS  Google Scholar 

  • Rao TK, Friedman EA, Nicastri AD (1987) The types of renal disease in the acquired immunodeficiency syndrome. N Engl J Med 316: 1062–1068

    Article  PubMed  CAS  Google Scholar 

  • Rappaport J, Kopp JB, Klotman PE (1994) Host virus interactions and the molecular regulation of HIV-1: Role in the pathogenesis of HIV-associated nephropathy. Kidney Int 46: 16–27

    Article  PubMed  CAS  Google Scholar 

  • Ray PE, Bruggeman LA, Weeks BS, Kopp JB, Bryant J, Owens JW, Notkins AL, Klotman PE (1994) bFGF and its low affinity receptors in the pathogenesis of HIV-associated nephropathy. Kidney Int 46: 759–772

    Article  PubMed  CAS  Google Scholar 

  • Sadaie MR, Tschader E, Valerie K, Rosenberg M, Felber BK, Pavlakis GN, Klotman ME, Wong-Staal F (1990) Activation of tat defective human immunodeficiency virus by ultraviolet light. New Biol 2: 479–486

    PubMed  CAS  Google Scholar 

  • Salomon B, Lores P, Pioche C, Racz P, Jami J, Klatzmann D (1994) Conditional ablation of dendritic cells in transgenic mice. J Immunol 152: 537–548

    PubMed  CAS  Google Scholar 

  • Santoro TJ, Bryant JL, Pellicoro J, Klotman ME, Kopp JB, Bruggeman LA, Franks RR, Notkins AL, Klotman PE (1994) Growth failure and AIDS-like cachexia syndrome in HIV-1 transgenic mice. Virology 201: 147–151

    Article  PubMed  CAS  Google Scholar 

  • Shirai A, Klinman DM (1993) Immunization with recombinant gp160 prolongs the survival of HIV-1 transgenic mice. AIDS Res Hum Retroviruses 9: 979–983

    Article  PubMed  CAS  Google Scholar 

  • Skowronski J (1991) Expression of a human immunodeficiency virus type 1 long terminal repeat/ simian virus 40 early region fusion gene in transgenic mice. J Virol 65: 754–762

    PubMed  CAS  Google Scholar 

  • Skowronski J, Parks D, Mariani R (1993) Altered T cell activation and development in transgenic mice expressing the HIV-1 nef gene. EMBO J 12: 703–713

    PubMed  CAS  Google Scholar 

  • Stein B, Rahmsdorf HJ, Steffen A, Litfin M, Herrlich P (1989) UV induced DNA damage is an intermediate step in UV induced expression of human immunodeficiency virus type I, collagenase, c-fos and metallothionein. Mol Cell Biol 9: 5169–5181

    PubMed  CAS  Google Scholar 

  • Toggas SM, Masliah E, Rockenstein EM, Rail GF, Abraham CR, Mucke L (1994) Central nervous system damage produced by expression of the HIV-1 coat protein gp120 in transgenic mice. Nature 367: 188–193

    Article  PubMed  CAS  Google Scholar 

  • Valerie K, Delers A, Bruck C, Thiriart C, Rosenberg H, Debouck C, Rosenberg M (1988) Activation of human immunodeficiency virus type I by DNA damage in human cells. Nature 333: 78–81

    Article  PubMed  CAS  Google Scholar 

  • Vogel J, Hinrichs SH, Reynolds RK, Luciw PA, Jay G (1988) The HIV tat gene induces dermal lesions resembling Kaposi’s sarcoma in transgenic mice. Nature 335: 606–611

    Article  PubMed  CAS  Google Scholar 

  • Vogel J, Hinrichs SH, Napolitano LA, Ngo L, Jay G (1991) Liver cancer in transgenic mice carrying the human immunodeficiency virus tat gene. Cancer Res. 51: 6686–6690

    PubMed  CAS  Google Scholar 

  • Vogel J, Cepeda M, Tschachler E, Napolitano LA, Jay G (1992) UV activation of human immunodeficiency virus gene expression in transgenic mice. J Virol 66: 1–5

    PubMed  CAS  Google Scholar 

  • Werner S, Hofschneider PH, Roth WK (1989) Cells derived from sporadic and AIDS-related Kaposi’s sarcoma reveal identical cytochemical and molecular properties in vitro. Int J Cancer 43: 1137–1144

    Article  PubMed  CAS  Google Scholar 

  • Zider A, Mashhour B, Fergelot P, Grimber G, Vernet M, Hazan U, Couton D, Briand P, Cavard C (1993) Dispensable role of the NF-kappa B sites in the UV-induction of the HIV-1 LTR in transgenic mice. Nucleic Acids Res 21: 79–86

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Mount Sinai Medical Center, Division of Nephrology, Box 1243, New York, NY, 10029, USA

    P. E. Klotman

  2. National Institute of Dental Research, Building 30, NIH, Bethesda, MD, 20892, USA

    A. L. Notkins

Authors
  1. P. E. Klotman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. L. Notkins
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Francis V. Chisari M.D. (Member, Head) (Member, Head)

  2. Division of Experimental Pathology, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Francis V. Chisari M.D. (Member, Head) (Member, Head)

  3. Department of Neuropharmacology, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Michael B. A. Oldstone M.D. (Member, Head) (Member, Head)

  4. Division of Virology, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Michael B. A. Oldstone M.D. (Member, Head) (Member, Head)

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Klotman, P.E., Notkins, A.L. (1996). Transgenic Models of Human Immunodeficiency Virus Type-1. In: Chisari, F.V., Oldstone, M.B.A. (eds) Transgenic Models of Human Viral and Immunological Disease. Current Topics in Microbiology and Immunology, vol 206. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-85208-4_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-85208-4_11

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-85210-7

  • Online ISBN: 978-3-642-85208-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation