Skip to main content

Advertisement

SpringerLink
Log in

Interaction of α-2-macroglobulin and HSV-1 during infection of neuronal cells

  • Published:
Journal of NeuroVirology Aims and scope Submit manuscript

Abstract

We describe the effect of pretreatment with alpha-2-macroglobulin (A2M) on the susceptibility of the human neuroblastoma SKNMC cell line to infection by herpes virus type 1 (HSV-1). ELISA and co-immunoprecipitation experiments confirmed the A2M-HSV-1 interaction in vitro. Indirect immunofluorescence shows that A2M exacerbated the cytopathic effect induced after HSV-1 infection. However, A2M-pretreated SKNMC cells notably produced fewer HSV-1 particles than did the untreated cells, suggesting that A2M could induce a restrictive infection. Furthermore, high levels of HSV-1 and A2M induced the production of nitric oxide (NO) in SKNMC. Preliminary results suggest that A2M might induce apoptosis in HSV-1-infected cells. These findings affirm the conclusion that A2M may interact directly with HSV-1 and modulate the course of the infection in SKNMC human neuroblastoma cells.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bishop SA, Hill TJ (1991). Herpes simplex virus infection and damage in the central nervous system: immunomodulation with adjuvant, cyclophosphamide and cyclosporin A. Arch Virol 116: 57–68.

    Article  CAS  PubMed  Google Scholar 

  • Blacker D, Wilcox MA, Laird NM, Rodes L, Horvath SM, Go RCP, Perry R, Watson B Jr, Bassett SS, McInnis MG, Albert MS, Hyman BT, Tanzi RE (1998). α2-Macroglobulin is genetically associated with Alzheimer’s disease. Nat Genet 19: 357–360.

    Article  CAS  PubMed  Google Scholar 

  • Borth W (1992). α2-Macroglobulin, a multifunctional binding protein with targeting characteristics. FASEB J 6: 3345–3353.

    CAS  PubMed  Google Scholar 

  • Bullido MJ, Artiga MJ, Recuero M, Sastre I, García MA, Aldudo J, Lendon C, Han SW, Morris JC, Frank A, Vázquez J, Goate A, Valdivieso F (1998). A polymorphism in the regulatory region of APOE associated with risk for Alzheimer’s dementia. Nat Genet 18: 69–71.

    Article  CAS  PubMed  Google Scholar 

  • Carr DJ, Campbell IL (1999). Transgenic expression of interleukin-6 in the central nervous system confers protection against acute herpes simplex virus type-1 infection. J Neuro Virol 5: 449–457.

    CAS  Google Scholar 

  • Chesnokova NB, Maichuk YF (1986). Antiproteases in herpetic keratitis. MPS 9: 593–596.

    CAS  Google Scholar 

  • Corder E, Lannfelt L, Mulder M (1998). Apolipoprotein E and herpes simplex virus 1 in Alzheimer’s disease. Lancet 352: 1312–1313.

    Article  CAS  PubMed  Google Scholar 

  • Cribbs DH, Azizeh BY, Cotman CW, LaFerla FM (2000). Fibril formation and neurotoxicity by a herpes simplex virus glycoprotein B fragment with homology to the Alzheimer’s Aβ peptide. Biochemistry 39: 5988–5994.

    Article  CAS  PubMed  Google Scholar 

  • de la Monte S, Lu B-X, Sohn Y-K, Etienne D, Kraft J, Ganju N, Wands JR (2000). Aberrant expression of nitric oxide synthase III in Alzheimer’s disease: relevance to cerebral vasculopathy and neurodegeneration. Neurobiol Aging 21: 309–319.

    Article  PubMed  Google Scholar 

  • Dow DJ, Lindsey N, Cairns NJ, Brayne C, Robinson D, Huppert FA, Paykel ES, Xuereb J, Wilcock G, Whittaker JL, Rubinsztein DC (1999). α2-Macroglobulin polymorphism and Alzheimer’s disease risk in the UK. Nat Genet 22: 16–17.

    Article  CAS  PubMed  Google Scholar 

  • Du Y, Bales KR, Dodel RC, Liu X, Glinn MA, Horn JW, Little SP, Paul SM (1998). α2-Macroglobulin attenuates β-amyloid peptide 1–40 fibril formation and associated neurotoxicity of cultured fetal rat cortical neurons. J Neurochem 70: 1182–1188.

    Article  CAS  PubMed  Google Scholar 

  • Dunn JT, Spiro R (1967). The α2-macroglobulin of human plasma. J Biol Chem 242: 5549–5555.

    CAS  PubMed  Google Scholar 

  • Fabrizi C, Businaro R, Lauro GM, Starace G, Fumagalli L (1999). Activated α2-macroglobulin increases β-amyloid (25–35)-induced toxicity in LAN5 human neuroblastoma cells. Exp Neurol 155: 252–259.

    Article  CAS  PubMed  Google Scholar 

  • Fujioka N, Akazawa R, Ohashi K, Fujii M, Ikeda M, Kurimoto M (1999). Interleukin-18 protects mice against acute herpes simplex virus type 1 infection. J Virol 73: 2401–2409.

    CAS  PubMed  Google Scholar 

  • Galvan V, Brandimarti R, Munger J, Roizman B (2000). Bcl-2 blocks a caspase-dependent pathway of apoptosis activated by herpes simplex virus 1 infection in Hep-2 cells. J Virol 74: 1931–1938.

    Article  CAS  PubMed  Google Scholar 

  • Galvan V, Brandimarti R, Roizman B (1999). Herpes simplex virus 1 blocks caspase-3-independent and caspase-dependent pathways to cell death. J Virol 73: 3219–3226.

    CAS  PubMed  Google Scholar 

  • Galvan V, Roizman B (1998). Herpes simplex virus 1 induces and blocks apoptosis at multiple steps during infection and protects cells from exogenous inducers in a cell-type-dependent manner. Proc Natl Acad Sci USA 95: 3931–3936.

    Article  CAS  PubMed  Google Scholar 

  • Ganter U, Strauss S, Jonas U, Weidemann A, Beyreuther K, Volk B, Berger M, Bauer J (1991). α2-Macroglobulin synthesis in interleukin-6-stimulated human neuronal (SH-SY5Y neuroblastoma) cells. FEBS Lett 282: 127–131.

    Article  CAS  PubMed  Google Scholar 

  • Geraghty RJ, Krummenacher C, Cohen GH, Eisenberg RJ, Spear PG (1998). Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor. Science 280: 1618–1620.

    Article  CAS  PubMed  Google Scholar 

  • Green LC, Wagner DA, Glogowsky J, Skipper PL, Wishnok JS, Tannenbaum JS (1982). Analysis of nitrate, nitric and (15N) nitrate in biological fluids. Anal Biochem 126: 131–136.

    Article  CAS  PubMed  Google Scholar 

  • Harpel P (1973). Studies on human plasma α2-macroglobulin-enzyme interactions. Evidence for proteolytic modification of the subunit chain structure. J Exp Med 138: 508–521.

    Article  CAS  PubMed  Google Scholar 

  • Immergluck LC, Domowicz MS, Schwartz NB, Herold BC (1998). Viral and cellular requirements for entry of herpes simplex virus type 1 into primary neuronal cells. J Gen Virol 79: 549–559.

    CAS  PubMed  Google Scholar 

  • Itabashi S, Arai H, Matsui T, Higuchi S, Sasaki H (1997). Herpes simplex virus and risk of Alzheimer’s disease. Lancet 349: 1102.

    Article  CAS  PubMed  Google Scholar 

  • Itzhaki R, Lin W-R, Shang D, Wilcock GK, Faragher B, Jamieson GA (1997). Herpes simplex virus type 1 in brain and risk of Alzheimer’s disease. Lancet 349: 241–244.

    Article  CAS  PubMed  Google Scholar 

  • Itzhaki RF, Lin W-R, Wilcock GK, Faragher B (1998). HSV-1 and risk of Alzheimer’s disease. Lancet 352: 238.

    Article  CAS  PubMed  Google Scholar 

  • Ji Z-S, Brecht WJ, Miranda RD, Hussain MM, Innerarity TI, Mahley RW (1993). Role of heparan sulfate proteoglycansin the binding and uptake of apolipoprotein E-enriched remnant lipoproteins by cultured cells. J Biol Chem 268: 10160–10167.

    CAS  PubMed  Google Scholar 

  • Jones C (1999). Alphaherpervirus latency: its role in disease and survival of the virus in nature. Adv Virus Bes 51: 81–133.

    Article  Google Scholar 

  • Komatsu T, Bi Z, Reiss CS (1996). Interferon-γ induced type I nitric oxide synthase activity inhibits viral replication in neurons. J Neuroimmunol 68: 101–108.

    Article  CAS  PubMed  Google Scholar 

  • Koyama AH, Miwa Y (1997). Suppression of apoptosis DNA fragmentation in herpes simplex virus type 1-infected cells. J Virol 71: 2567–2571.

    CAS  PubMed  Google Scholar 

  • Krimbou L, Tremblay M, Davignon J, Cohn JS (1998). Association of apolipoprotein E with α2-macroglobulin in human plasma. J Lipid Res 39: 2373–2386.

    CAS  PubMed  Google Scholar 

  • Krüger R, Menezes-Saecker AMV, Schöls L, Kuhn W, Müller T, Woitalla D, Berg D, Berger K, Przuntek H, Epplen JT, Riess O (2000). Genetic analysis of the α2-macroglobulin gene in early- and late-onset Parkinson’s disease. Neuroreport 11: 2439–2442.

    Article  PubMed  Google Scholar 

  • Laxminarayana R, Devireddy R, Jones CJ (1999). Activation of caspases and p53 by bovine herpesvirus 1 infection results in programmed cell death and efficient virus release. J Virol 73: 3778–3788.

    Google Scholar 

  • LeBlanc RA, Pesnicak L, Cabral ES, Godleski M, Straus SE (1999). Lack of interleukin-6 (IL-6) enhances susceptibility to infection but does not alter latency or reactivation of herpes simplex virus type 1 in IL-6 knockout mice. J Virol 73: 8145–8151.

    CAS  PubMed  Google Scholar 

  • Leissring MA, Sugarman MC, LaFerla FM (1998). Herpes simplex virus infections and Alzheimer’s disease. Drugs Aging 13: 193–198.

    Article  CAS  PubMed  Google Scholar 

  • López-Guerrero JA, Alonso MA (1997). Nitric oxide production induced by herpes simplex virus type 1 does not alterthe course of the infection in human monocytic cells. J Gen Virol 78: 1977–1980.

    PubMed  Google Scholar 

  • López-Guerrero JA, Alonso M, Martín-Belmonte F, Carrasco L (2000). Poliovirus induces apoptosis in the human U937 promonocytic cell line. Virology 272: 250–256.

    Article  PubMed  Google Scholar 

  • López-Guerrero JA, Carrasco L (1998). Effect of nitric oxide on poliovirus infection of two human cell lines. J Virol 72: 2538–2540.

    PubMed  Google Scholar 

  • Moestrup SK (1994). The α2-macroglobulin receptor and epithelial glycoprotein-330: two giant receptors mediating endocytosis of multiple ligands. Biochim Biophys Acta 1197: 197–213.

    CAS  PubMed  Google Scholar 

  • Pritchett TJ, Paulson JC (1989). Basis for the potent inhibition of influenza virus infection by equine and guinea pig α2-macroglobulin. J Biol Chem 264: 9850–9858.

    CAS  PubMed  Google Scholar 

  • Qiu X, Abdel-Meguid SS (1999). Human herpesvirus proteases. In: Proteases of infectious agents. Academic Press: New York, pp 93–115.

    Chapter  Google Scholar 

  • Qiu Z, Strickland DK, Hyman BT, Rebeck GW (1999). α2-Macroglobulin enhances the clearance of endogenous soluble β-amyloid peptide via low-density lipoprotein receptor-relatedprotein in cortical neurons. J Neurochem 73: 1393–1398.

    Article  CAS  PubMed  Google Scholar 

  • Romero F, Martínez-A C, Camonis J, Rebollo A (1999). Aiolos transcription factor controls cell death in T cells by regulating Bcl-2 expression and its cellular localization. EMBO J 18: 3419–3430.

    Article  CAS  PubMed  Google Scholar 

  • Rudrasingham V, Vrièze FW-D, Lambert J-C, Chakraverty S, Kehoe P, Crook R, Amouyel P, Wu W, Rice F, Pérez-Tur J, Frigard B, Morris JC, Carty S, Petersen R, Cottel D, Tunstall N, Holmans P, Lovestone S, Chartier-Harlin M-C, Goate A, Hardy J, Owen MJ, Williams J (1999). α2-Macroglobulingene and Alzheimer’s disease. Nat Genet 22: 17–19.

    Article  PubMed  Google Scholar 

  • Sheaffer A, Newcomb WW, Brown JC, Gao M, Weller SK, Tenney DJ (2000). Evidence for controlled incorporation of herpes simplex virus type 1 UL26 protease into capsids. J Virol 74: 6838–6848.

    Article  CAS  PubMed  Google Scholar 

  • Shukla D, Rowe CL, Dong Y, Racaniello VR, Spear PG (1999). The murine homolog (Mph) of human herpesvirus entry protein B (HveB) mediates entry of pseudorabies virus but not herpes simplex virus type 1 and 2. J Virol 73: 4493–4497.

    CAS  PubMed  Google Scholar 

  • Singleton AB, Gibson AM, McKeith IG, Ballard CA, Perry RH, Ince PG, Edwardson JA, Morris CM (1999). α2-Macroglobulin polymorphisms in Alzheimer’s disease and dementia with Lewy bodies. Neuroreport 10: 1507–1510.

    Article  CAS  PubMed  Google Scholar 

  • Soker S, Svahn CM, Neufeld G (1993). Vascular endothelial growth factor is inactivated by binding to α2-macroglobulin and the binding is inhibited by heparin. J Biol Chem 268: 7685–7691.

    CAS  PubMed  Google Scholar 

  • Sottrup-Jensen L (1989). α2-Macroglobulin: structure, shape, and mechanism of proteinase complex formation. J Biol Chem 264: 11539–11543.

    CAS  PubMed  Google Scholar 

  • Strauss S, Bauer J, Ganter U, Jonas U, Berger M, Volk B (1992). Detection of interleukin-6 and α2-macroglobulin immunoreactivity in cortex and hippocampus of Alzheimer’s disease patients. Lab Invest 66: 223–230.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center of Molecular Biology Severo Ochoa, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain

    María Alonso, Ana Dimitrijevic, María Recuero, Elena Serrano, Fernando Valdivieso & José Antonio López-Guerrero

Authors
  1. María Alonso
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ana Dimitrijevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. María Recuero
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elena Serrano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fernando Valdivieso
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. José Antonio López-Guerrero
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to José Antonio López-Guerrero.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alonso, M., Dimitrijevic, A., Recuero, M. et al. Interaction of α-2-macroglobulin and HSV-1 during infection of neuronal cells. Journal of NeuroVirology 7, 556–563 (2001). https://doi.org/10.1080/135502801753248141

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1080/135502801753248141

Keywords

Search

Navigation