Abstract
To determine whether rabies viruses replicate in macrophage or macrophage-like cells, several human and murine macrophage-like cell lines, as well as primary cultures of murine bone marrow macrophages, were incubated with the Evelyn-Rokitnicki-Abelseth (ERA) virus and several different street rabies viruses (SRV). ERA rabies virus replicated well in human monocytic U937 and THP-1 cells and murine macrophage IC-21 cells, as well as primary cultures of murine macrophages. Minimal replication was detected in murine monocytic WEHI-3BD- and PU5-1R cells, and ERA virus did not replicate in murine monocytic P388D1 or J774A.1 cells. A tissue culture-adapted SRV of bat origin also replicated in IC-21 and U937 cells. Non-tissue culture-adapted SRV isolated from different animal species, particularly bats, replicated minimally in U937, THP-1, IC-21 cells and primary murine bone marrow macrophages. To determine whether rabies virus replication is dependent upon the state of differentiation of the macrophage-like cell, human promyelocytic HL-60 cells were differentiated with 12-O-tetradecanoylphorbol-13-acetate (TPA). ERA rabies virus replicated in the differentiated HL-60 cells but not in undifferentiated HL-60 cells. Persistent infections were established in macrophage-like U937 cells with ERA rabies virus and SRV, and infectious SRV was isolated from adherent bone marrow cells of mice that had been infected 96 days previously. Virus harvested from persistently infected U937 cells and the adherent bone marrow cells had specifically adapted to each cell. This specificity was shown by the inability of the viruses to infect macrophages other than U937 cells and primary bone marrow macrophages, respectively. Virus titers of the persistently infected U937 cells fluctuated with extended cell passage. After 30 passages, virus released from the cells had lost virulence as shown by its inability to kill intracranially inoculated mice. However, the avirulent virus released from the persistently infected cells was more efficient in infecting and replicating in naive U937 cells than the virus which was used to establish the persistent infection. These results suggest that macrophages may serve as reservoirs of infection in vivo, sequestering virus which may subsequently be activated from its persistent state, resulting in clinical infection and death.
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- Ackerman J. J., Duerre J. A. Long-term culturing of TPA-induced differentiated HL-60 cells results in increased levels of lytic enzymes. Exp Cell Res. 1989 Aug;183(2):353–360. doi: 10.1016/0014-4827(89)90396-0. [DOI] [PubMed] [Google Scholar]
- Aghomo H. O., Rupprecht C. E. Further studies on rabies virus isolated from healthy dogs in Nigeria. Vet Microbiol. 1990 Mar;22(1):17–22. doi: 10.1016/0378-1135(90)90120-k. [DOI] [PubMed] [Google Scholar]
- Andzhaparidze O. G., Bogomolova N. N., Boriskin Y. S., Bektemirova M. S., Drynov I. D. Comparative study of rabies virus persistence in human and hamster cell lines. J Virol. 1981 Jan;37(1):1–6. doi: 10.1128/jvi.37.1.1-6.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Armstrong J. A. Cytopathic effect inhibition assay for interferon: microculture plate assay. Methods Enzymol. 1981;78(Pt A):381–387. doi: 10.1016/0076-6879(81)78145-x. [DOI] [PubMed] [Google Scholar]
- Babior B. M. The respiratory burst of phagocytes. J Clin Invest. 1984 Mar;73(3):599–601. doi: 10.1172/JCI111249. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Belardelli F., Vignaux F., Proietti E., Gresser I. Injection of mice with antibody to interferon renders peritoneal macrophages permissive for vesicular stomatitis virus and encephalomyocarditis virus. Proc Natl Acad Sci U S A. 1984 Jan;81(2):602–606. doi: 10.1073/pnas.81.2.602. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Czub M., Czub S., McAtee F. J., Portis J. L. Age-dependent resistance to murine retrovirus-induced spongiform neurodegeneration results from central nervous system-specific restriction of virus replication. J Virol. 1991 May;65(5):2539–2544. doi: 10.1128/jvi.65.5.2539-2544.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Folks T. M., Justement J., Kinter A., Dinarello C. A., Fauci A. S. Cytokine-induced expression of HIV-1 in a chronically infected promonocyte cell line. Science. 1987 Nov 6;238(4828):800–802. doi: 10.1126/science.3313729. [DOI] [PubMed] [Google Scholar]
- Folks T. M., Justement J., Kinter A., Schnittman S., Orenstein J., Poli G., Fauci A. S. Characterization of a promonocyte clone chronically infected with HIV and inducible by 13-phorbol-12-myristate acetate. J Immunol. 1988 Feb 15;140(4):1117–1122. [PubMed] [Google Scholar]
- Gendelman H. E., Narayan O., Kennedy-Stoskopf S., Kennedy P. G., Ghotbi Z., Clements J. E., Stanley J., Pezeshkpour G. Tropism of sheep lentiviruses for monocytes: susceptibility to infection and virus gene expression increase during maturation of monocytes to macrophages. J Virol. 1986 Apr;58(1):67–74. doi: 10.1128/jvi.58.1.67-74.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gendelman H. E., Narayan O., Molineaux S., Clements J. E., Ghotbi Z. Slow, persistent replication of lentiviruses: role of tissue macrophages and macrophage precursors in bone marrow. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7086–7090. doi: 10.1073/pnas.82.20.7086. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gendelman H. E., Orenstein J. M., Baca L. M., Weiser B., Burger H., Kalter D. C., Meltzer M. S. The macrophage in the persistence and pathogenesis of HIV infection. AIDS. 1989 Aug;3(8):475–495. doi: 10.1097/00002030-198908000-00001. [DOI] [PubMed] [Google Scholar]
- Ibanez C. E., Schrier R., Ghazal P., Wiley C., Nelson J. A. Human cytomegalovirus productively infects primary differentiated macrophages. J Virol. 1991 Dec;65(12):6581–6588. doi: 10.1128/jvi.65.12.6581-6588.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kanno H., Wolfinbarger J. B., Bloom M. E. Aleutian mink disease parvovirus infection of mink peritoneal macrophages and human macrophage cell lines. J Virol. 1993 Apr;67(4):2075–2082. doi: 10.1128/jvi.67.4.2075-2082.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kawai A., Matsumoto S., Tanabe K. Characterization of rabies viruses recovered from persistently infected BHK cells. Virology. 1975 Oct;67(2):520–533. doi: 10.1016/0042-6822(75)90452-3. [DOI] [PubMed] [Google Scholar]
- King A. A., Sands J. J., Porterfield J. S. Antibody-mediated enhancement of rabies virus infection in a mouse macrophage cell line (P388D1). J Gen Virol. 1984 Jun;65(Pt 6):1091–1093. doi: 10.1099/0022-1317-65-6-1091. [DOI] [PubMed] [Google Scholar]
- King C. C., de Fries R., Kolhekar S. R., Ahmed R. In vivo selection of lymphocyte-tropic and macrophage-tropic variants of lymphocytic choriomeningitis virus during persistent infection. J Virol. 1990 Nov;64(11):5611–5616. doi: 10.1128/jvi.64.11.5611-5616.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koren H. S., Handwerger B. S., Wunderlich J. R. Identification of macrophage-like characteristics in a cultured murine tumor line. J Immunol. 1975 Feb;114(2 Pt 2):894–897. [PubMed] [Google Scholar]
- Lodmell D. L., Arai Y. T., Ewalt L. C. Influence of cell type and virus upon lysis of rabies virus-infected cells by antibody and complement. Arch Virol. 1981;70(2):147–155. doi: 10.1007/BF01315008. [DOI] [PubMed] [Google Scholar]
- Lodmell D. L., Ewalt L. C. Pathogenesis of street rabies virus infections in resistant and susceptible strains of mice. J Virol. 1985 Sep;55(3):788–795. doi: 10.1128/jvi.55.3.788-795.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lodmell D. L. Genetic control of resistance to street rabies virus in mice. J Exp Med. 1983 Feb 1;157(2):451–460. doi: 10.1084/jem.157.2.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lodmell D. L., Wiedbrauk D. L., Ewalt L. C. Interferon induced within the central nervous system during infection is inconsequential as a mechanism responsible for murine resistance to street rabies virus. J Gen Virol. 1989 Feb;70(Pt 2):473–478. doi: 10.1099/0022-1317-70-2-473. [DOI] [PubMed] [Google Scholar]
- Macé K., Duc Dodon M., Gazzolo L. Restriction of HIV-1 replication in promonocytic cells: a role for IFN-alpha. Virology. 1989 Feb;168(2):399–405. doi: 10.1016/0042-6822(89)90282-1. [DOI] [PubMed] [Google Scholar]
- Metcalf D., Nicola N. A. Autoinduction of differentiation in WEHI-3B leukemia cells. Int J Cancer. 1982 Dec 15;30(6):773–780. doi: 10.1002/ijc.2910300616. [DOI] [PubMed] [Google Scholar]
- Metcalf D. The molecular biology and functions of the granulocyte-macrophage colony-stimulating factors. Blood. 1986 Feb;67(2):257–267. [PubMed] [Google Scholar]
- Minta J. O., Pambrun L. In vitro induction of cytologic and functional differentiation of the immature human monocytelike cell line U-937 with phorbol myristate acetate. Am J Pathol. 1985 Apr;119(1):111–126. [PMC free article] [PubMed] [Google Scholar]
- Murphy F. A., Bauer S. P. Early street rabies virus infection in striated muscle and later progression to the central nervous system. Intervirology. 1974;3(4):256–268. doi: 10.1159/000149762. [DOI] [PubMed] [Google Scholar]
- Reiser H., Kühn J., Doerr H. W., Kirchner H., Munk K., Braun R. Human cytomegalovirus replicates in primary human bone marrow cells. J Gen Virol. 1986 Dec;67(Pt 12):2595–2604. doi: 10.1099/0022-1317-67-12-2595. [DOI] [PubMed] [Google Scholar]
- Shih D. S., Carruth L. M., Anderson M., Clements J. E. Involvement of FOS and JUN in the activation of visna virus gene expression in macrophages through an AP-1 site in the viral LTR. Virology. 1992 Sep;190(1):84–91. doi: 10.1016/0042-6822(92)91194-y. [DOI] [PubMed] [Google Scholar]
- Sitbon M., Nishio J., Wehrly K., Lodmell D., Chesebro B. Use of a focal immunofluorescence assay on live cells for quantitation of retroviruses: distinction of host range classes in virus mixtures and biological cloning of dual-tropic murine leukemia viruses. Virology. 1985 Feb;141(1):110–118. doi: 10.1016/0042-6822(85)90187-4. [DOI] [PubMed] [Google Scholar]
- Smith J. S., Fishbein D. B., Rupprecht C. E., Clark K. Unexplained rabies in three immigrants in the United States. A virologic investigation. N Engl J Med. 1991 Jan 24;324(4):205–211. doi: 10.1056/NEJM199101243240401. [DOI] [PubMed] [Google Scholar]
- Smith J. S., Orciari L. A., Yager P. A., Seidel H. D., Warner C. K. Epidemiologic and historical relationships among 87 rabies virus isolates as determined by limited sequence analysis. J Infect Dis. 1992 Aug;166(2):296–307. doi: 10.1093/infdis/166.2.296. [DOI] [PubMed] [Google Scholar]
- Smith J. S., Seidel H. D. Rabies: a new look at an old disease. Prog Med Virol. 1993;40:82–106. [PubMed] [Google Scholar]
- Tsuchiya S., Kobayashi Y., Goto Y., Okumura H., Nakae S., Konno T., Tada K. Induction of maturation in cultured human monocytic leukemia cells by a phorbol diester. Cancer Res. 1982 Apr;42(4):1530–1536. [PubMed] [Google Scholar]
- Turner G. S., Ballard R. Interaction of mouse peritoneal macrophages with fixed rabies virus in vivo and in vitro. J Gen Virol. 1976 Feb;30(2):223–231. doi: 10.1099/0022-1317-30-2-223. [DOI] [PubMed] [Google Scholar]
- Walker W. S., Gandour D. M. Detection and functional assessment of complement receptors on two murine macrophage-like cell lines. Exp Cell Res. 1980 Sep;129(1):15–21. doi: 10.1016/0014-4827(80)90326-2. [DOI] [PubMed] [Google Scholar]
- Weinshenker B. G., Wilton S., Rice G. P. Phorbol ester-induced differentiation permits productive human cytomegalovirus infection in a monocytic cell line. J Immunol. 1988 Mar 1;140(5):1625–1631. [PubMed] [Google Scholar]
- Wu L., Morahan P. S., Leary K. Mechanisms of intrinsic macrophage--virus interactions in vitro. Microb Pathog. 1990 Nov;9(5):293–301. doi: 10.1016/0882-4010(90)90064-w. [DOI] [PubMed] [Google Scholar]