Summary
Estramustine phosphate, an estradiol-mustard conjugate, was shown to reversibly inhibit a stage during the first hour of productive adenovirus 2 infection of HeLa cells. This drug, employed in the therapy of advanced prostatic cancer, specifically interacts with microtubule-associated proteins (MAPs) of the cytoskeleton. The results obtained under physiological conditions in vivo suggest a MAPs-interference with the microtubule-mediated vectorial migration of the virus inoculum to the nucleus. Virus attachment, uncoating kinetics and the appearance of established uncoating intermediates were not affected.
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References
Babiss LE, Luftig RB, Weatherbee JA, Weihing RR, Ray UR, Fields BN (1979) Reovirus serotypes 1 and 3 differ in their in vitro association with microtubules. J Virol 30: 863–874
Ball EH, Singer SJ (1981) Association of microtubules and intermediate filaments in normal fibroblasts and its disruption upon transformation by a temperature-sensitive mutant of Rous sarcoma virus. Proc Natl Acad Sci USA 78: 6986–6990
Belin M-T, Boulanger P (1985) Cytoskeletal proteins associated with intracytoplasmic human adenovirus at an early stage of infection. Exp Cell Res 160: 356–370
Belin M-T, Boulanger P (1987) Processing of vimentin occurs during the early stages of adenovirus infection. J Virol 61: 2559–2566
Brinkley BR (1982) Summary: organization of the cytoplasm. Cold Spring Harb Symp Quant Biol 46: 1029–1040
Brown DT, Burlingham BT (1973) Penetration of host cell membranes by adenovirus 2. J Virol 12: 386–396
Chardonnet Y, Dales S (1970) Early events in the interaction of adenoviruses with HeLa cells. I. Penetration of type 5 and intracellular release of the DNA genome. Virology 40: 462–477
Dales S, Chardonnet Y (1973) Early events in the interaction of adenoviruses with HeLa cells. IV. Association with microtubules and the nuclear pore complex during vectorial movement of the inoculum. Virology 56: 465–483
Edmondson JM, Armstrong LS, Martinez AO (1988) A rapid and simple MTT-based spectrophotometric assay for determining drug sensitivity in monolayer cultures. J Tissue Cult Methods 11: 15–17
Everitt E, Meador SA, Levine AS (1977) Synthesis and processing of the precursor to the major core protein of adenovirus type 2. J Virol 21: 199–214
Everitt E, Sundquist B, Philipson L (1971) Mechanism of the arginine requirement for adenovirus synthesis. I. Synthesis of structural proteins. J Virol 8: 742–753
Everitt E, Svensson U, Wohlfart C, Persson P (1986) Requirements for initial adenovirus uncoating and internalization. In: Crowell R, Lonberg-Holm K (eds) Virus attachment and entry into cells. American Society for Microbiology, Washington, DC, pp 196–204
FitzGerald DJP, Padmanabhan R, Pastan I, Willingham MC (1983) Adenovirus-induced release of epidermal growth factor and Pseudomonas toxin into the cytosol of KB cells during receptor-mediated endocytosis. Cell 32: 607–617
Fridén B, Wallin M, Deinum J, Prasad V, Luduena R (1987) Effect of estramustine phosphate on the assembly of trypsin-treated microtubules and microtubules reconstituted from purified tubulin with either tau, MAP 2, or the tubulin-binding fragment of MAP 2. Arch Biochem Biophys 257: 123–130
Hartley-Asp B (1984) Estramustine-induced mitotic arrest in two human prostatic carcinoma cell lines DU 145 and PC-3. Prostate 5: 93–100
Hartley-Asp B, Gunnarsson PO (1982) Growth and cell survival following treatment with estramustine, nor-nitrogen mustard, estradiol and testosterone of a human prostatic cancer cell line (DU 145). J Urol 127: 818–822
Jackson P, Bellet AJD (1985) Reduced microfilament organization in adenovirus type 5-infected rat embryo cells: a function of early region 1 a. J Virol 55: 644–650
Jönsson G, Högberg B, Nilsson T (1977) Treatment of advanced prostate carcinoma with estramustine phosphate (Estracyt®). Stand J Urol Nephrol 11: 231–238
Lawrence WC, Ginsberg HS (1967) Intracellular uncoating of type 5 adenovirus deoxyribonucleic acid. J Virol 1: 851–867
Lazarides E (1980) Intermediate filaments as mechanical integrators of cellular space. Nature 283: 249–256
Lenk R, Storch T, Maizel JV Jr (1980) Cell architecture during adenovirus infection. Virology 105: 19–34
Lonberg-Holm K, Philipson L (1969) Early events of virus-cell interaction in an adenovirus system. J Virol 4: 323–338
Luftig RB, Weihing RR (1975) Adenovirus binds to rat brain microtubules in vitro. J Vitrol 16: 696–706
Lyon M, Chardonnet Y, Dales S (1978) Early events in the interaction of adenoviruses with HeLa cells. V. Polypeptides associated with the penetrating inoculum. Virology 87: 81–88
Maizel JV Jr, White DO, Scharff MD (1968) The polypeptides of adenovirus. I. Evidence for multiple components in the virion and a comparison of types 2, 7 A, and 12. Virology 36: 115–125
Mareel MM, Storme GA, Dragonetti CH, De Bruyne GK, Hartley-Asp B, Segers JL, Rabaey ML (1988) Antiinvasive activity of estramustine on malignant MO4 mouse cells and on DU-145 human prostate carcinoma cells in vitro. Cancer Res 48: 1842–1849
Miles BD, Luftig, RB, Weatherbee JA, Weihing RR, Weber J (1980) Quantification of the interaction between adenovirus types 2 and 5 and microtubules inside infected cells. Virology 105: 265–269
Morgan C, Rosenkranz HS, Mednis B (1969) Structure and development of viruses as observed in the electron microscope. X. Entry and uncoating of adenovirus. J Virol 4: 777–796
Nelson WJ, Traub P (1982) Intermediate (10 nm) filament proteins and the Ca2+-activated proteinase specific for vimentin and desmin in the cells from fish to man: an example of evolutionary conservation. J Cell Sci 57: 25–49
Osborn M, Geisler N, Shaw G, Sharp G, Weber K (1981) Intermediate filaments. Cold Spring Harb Symp Quant Biol 46: 413–429
Patterson S, Russell WC (1983) Ultrastructural and immunofluorescence studies of early events in adenovirus-HeLa cell interactions. J Gen Virol 64: 1091–1099
Penman S (1986) Virus metabolism and cellular architecture. In: Fields BN, Knipe DM (eds) Fundamental virology. Raven Press, New York, pp 169–182
Persson R, Svensson U, Everitt E (1983) Virus receptor interaction in the adenovirus system. II. Capping and cooperative binding of virions on HeLa cells. J Virol 46: 956–963
Philipson L (1967) Attachment and eclipse of adenovirus. J Virol 1: 868–875
Philipson L, Lonberg-Holm K, Pettersson U (1968) Virus-receptor interaction in an adenovirus system. J Virol 2: 1064–1075
Seth P, FitzGerald D, Ginsberg H, Willingham M, Pastan I (1984) Evidence that the penton base of adenovirus is involved in potentiation of toxicity of Pseudomonas exotoxin conjugated to epidermal growth factor. Mol Cell Biol 4: 1528–1533
Seth P, FitzGerald DJP, Willingham MC, Pastan I (1984) Role of low-pH environment in adenovirus enhancement of the toxicity of a Pseudomonas exotoxin-epidermal growth factor conjugate. J Virol 51: 650–655
Staufenbiel M, Epple P, Deppert W (1986) Progressive reorganization of the host cell cytoskeleton during adenovirus infection. J Virol 60: 1186–1191
Stearns ME, Wang M (1987) Polarized pigment granule transport occurs in the absence of microtubules in squirrelfish erythrophores: studies of the effects of estramustine. J Cell Sci 87: 565–580
Stearns ME, Wang M, Tew KD, Binder LI (1988) Estramustine binds a MAP-1-like protein to inhibit microtubule assembly in vitro and disrupt microtubule organization in DU 145 cells. J Cell Biol 107: 2647–2656
Svensson U (1985) Role of vesicles during adenovirus 2 internalization into HeLa cells. J Virol 55: 442–449
Svensson U, Persson R (1984) Entry of adenovirus 2 into HeLa cells. J Virol 51: 687–694
Svensson U, Persson P, Everitt E (1981) Virus-receptor interaction in the adenovirus system. I. Identification of virion attachment proteins of the HeLa cell plasma membrane. J Virol 38: 70–81
Vallee RB, Borisy GG (1977) Removal of the projections from cytoplasmic microtubules in vitro by digestion with trypsin. J Biol Chem 252: 377–382
Wallin M, Deinum J, Fridén B (1985) Interaction of estramustine phosphate with microtubule-associated proteins. FEBS Lett 179: 289–293
Weatherbee JA, Luftig RB, Weihing RR (1977) Binding of adenovirus to microtubules. II. Depletion of high-molecular-weight microtubule-associated protein content reduces specificity of in vitro binding. J Virol 21: 732–742
Wohlfart C (1988) Neutralization of adenoviruses: kinetics, stoichiometry, and mechanisms. J Virol 62: 2321–2328
Wohlfart CEG, Everitt E (1985) Assessment of specific virus infectivity and virus neutralization by a progeny virus immunotitration method as exemplified in an adenovirus system. J Virol Methods 11: 241–251
Wohlfart CEG, Svensson UK, Everitt E (1985) Interaction between HeLa cells and adenovirus type 2 virions neutralized by different antisera. J Virol 56: 896–903
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Everitt, E., Ekstrand, H., Boberg, B. et al. Estramustine phosphate reversibly inhibits an early stage during adenovirus replication. Archives of Virology 111, 15–28 (1990). https://doi.org/10.1007/BF01310502
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DOI: https://doi.org/10.1007/BF01310502