J Biomed 25, 1996 16, 1996 Roskilde University Interactions between * - PDF document

J Biomed 25, 1996 16, 1996 Roskilde University Interactions between * eoooomo*,m *e ooze • viral particles. [ 12], [ 12] [81 ] which can development of evidence that they of inducing inducing 67, 77]. Most importantly, they can interact with exoge- nous counterparts through a number of different mecha- nisms. In the following, the nature of these interactions and their consequences are discussed. The aim development and within the the Of note, endogenous proviruses are able to protect against infections with exogenous retroviruses retroviruses However, this is not the only mechanism of importance. Thus, an through binding binding This interferes with the tors resulting resulting 21, 22] and cats [58]. Also chickens harbor endogenous retroviruses involved in re- ceptor interference [65, 69, 75]. Most likely, the primary function of these avian endogenous retroviruses is to pre- vent reintegration of replication-competent endogenous retroviruses into the host chromosomes [69, 75]. by an an The Fv-4 gene, detected in populations of wild mice, controls the susceptibility to infections with ecotropic MuLVs [21, 22]. 22]. This glycoprotein seems to be factor acting with mice mice Another gene in mice, namely Rrncf has been associat- ed with a restriction in the replication of the polytropic MuLVs [6-8]. The Rmcfresistance allele is presumably also an endogenous retrovirus encoding for a glycoprotein which confers protection by competition for retroviral receptors [6, 7]. 7]. The degree of resistance against a retroviral infection conferred by receptor interference seems to be be i, 50]. Consequently, information about the transcriptional regulation of these genes would be valuable to to This also seems to be [ 12]. 12]. However, the sequences characterized thus far do not seem to genome, encoding interference can Sci 1997;4:1-8 41 ]. Moreover, evidence has been pro- vided that susceptible cells are able to take up the Fv-4 antigen from serum resulting in a reduced attachment of Friend virions to these cells [41]. Consequently, there is no need for the Fv-4 resistance allele to be expressed expressed This gene confers resistance to MuLV infections by clues to susceptibility to to Whether an Fv-l-like resistance mechanism is involved in this is an interesting possibility. Recombination Retroviruses are characterized by a high frequency of recombination [51 ]. Accordingly, this mechanism of com- bining genetic information is believed to play an impor- tant role in the evolution of retroviruses although the repair of defects probably is the most important function of retroviral recombination [80]. Normally, virions of retroviruses contain two identical identical mechanisms of retroviral recombination, see 32, 78]. Recombinations with single as well as multiple crossovers in different regions of the retroviral genomes resulting in over that that and references therein]. In addition polytrop- ic MuLVs have been isolated from mice mice In cats recombinants between feline leukemia virus (FeLV) and endogenous FeLV-like sequences seem to be be 71, 72]. More- over, recent findings that a considerable number of tu- mors induced by mouse mammary tumor viruses (MMTVs) contain recombinants recombinants Apparently, an invading retrovirus [ 10]. 10]. Recombination between exogenous and endogenous retroviruses could have significant immunological conse- quences. Of note, studies in mice [66, 83] as well as cats [71 ] have indicated that viral progenies lacking neutraliz- ing epitopes emerge upon recombination between an invading retrovirus and endogenous counterparts. Per- haps this this These recombinations involved the MAIDS virus gag gene which encodes for a compo- nent with a superantigen activity [33], and their detection raises the question of whether the generation of new superantigen specificities by recombination is implicated in the pathogenesis of MAIDS. Another aspect is that endogenous retroviruses are capable of repairing defects in exogenous ruses by by review, see 13, 30]. 30]. Furthermore, recombinations between con- taminating replication-competent viruses in the vector preparation and endogenous retroviruses of the recipient are a possibility [16]. Another safety aspect, although of minor importance, concerns the possibility of recombina- tion between endogenous retroviruses of the target cells and the the A lack in human organs for transplantations has fo- cused interest upon the possibility of using xenografts from primates and pigs. However, xenotransplantation involves introduction of 'foreign' endogenous retrovi- ruses into a new host. This entails a risk of recombination between these retroviruses and the 'native' endogenous retroviruses of the recipient [74]. Of note, several animal species, including baboons and their close relatives, carry endogenous retroviruses which have the potential of being expressed as particles [81 ], i.e. a cells [44, 68] 68] Obviously, the expression of a variety of different endoge- nous retroviral transcripts provides a rich and diverse source for recombinational exchange of genetic informa- tion with exogenous retroviruses. tween the envelope glycoproteins of the invading virus and the corresponding cell surface receptors. Consequent- ly, the formation of viral particles containing envelope glycoproteins encoded by another virus may provide these particles with a novel host cell tropism. Phenotypic mixing between distantly distantly There are several observations of phenotypic mixing be- tween endogenous and exogenous retroviruses. For exam- ple, HIV is capable of utilizing surface glycoproteins from endogenous MuLVs resulting in the appearance of pseu- dotypes with a novel host cell range, including CD4- cells and various animal cells [9, 47, 55, 76]. There is also an accelerated replication of HIV in CD4+ cells coinfected with MuLVs, perhaps reflecting a more efficient adsorp- tion of HIV pseudotypes to the target cells [9, with envelope questions with with an ing for provirus by with an the formation formation In the extreme, viral genomes are packaged into mixing helper helper This is also known as complementation. The initial step of a retroviral infection involves interactions be- Immunological Self-Tolerance, Epitope Restriction and Antigenic Mimicry Antibodies against various endogenous type C retrovi- ruses are naturally occurring various inbred inbred 49, 62]. Natural antibodies antibodies The specificity of these antibodies are restricted to epi- topes on the surface glycoprotein and the [18, 34] to be Sci 1997;4:1-8 gene products. retroviral antibodies antibodies Reactivity against one or a few of the major antigens of HTLV [46] and HIV HIV 82], most frequently gag gene products, is detectable in a relatively small fraction of sera from healthy humans with no other evidence of having a retroviral infection. Most likely, some of these seroinde- terminate reactivities are due to autoantibodies directed directed 82]. This assump- tion is supported by observations that a protein, encoded by an HTLV-related human endogenous retrovirus, may act as an autoantigen [4]. The genomes of retroviruses contain conserved stretches. In particular, certain stretches within the po/ gene are conserved conserved 61] but also a stretch in the trans- membrane protein seems to be subjected to a limited degree of variation between between There is evidence that the occurrence of identical or relat- ed epitopes between endogenous and exogenous retrovi- ruses results in a restricted ability to to Observations with avian leukosis viruses indicate that endogenous retroviruses interfere with with 85]. Briefly, the envelope glycoproteins of endoge- nous avian leukosis viruses contain epitopes which are also present in the exogenous avian leukosis/sarcoma carrying these these 82]. A breakdown of self-tolerance through antigenic mimi- cry may occur if an infectious agent from but host epitopes epitopes Whether exogenous re- troviruses are capable of inducing autoimmunity as a result of an antigenic relationship known. Recently, Recently, Autoim- mune diseases were not observed in these rats, but they responded with the production of antibodies possessing a reactivity to proteins encoded by their own endogenous retroviruses. Interestingly, These autoanti- autoanti- Future studies might reveal whether autoimmune responses against troviral antigens [2, 56]. ious bacterial several viruses [2, 56], 56], and HIV [48] have been linked with tigen activity. have only only although human T cells respond to MMTV superantigens [45]. Recently, isolation of a human endog- enous retroviral sequence perhaps encoding for a superan- tigen was reported [36], but confirmation of its biological activity is needed. Exogenous MMTVs are transmitted by the milk. After having crossed the gut of the suckling mouse, they infect susceptible target cells, presumably B cells in the Peyer patches [28, 39]. Most likely, the next steps in the estab- lishment of the infection involve expression of viral super- antigen on the surface of the infected cells resulting in stimulation and activation of T cells with the appropriate V[3 chains. These stimulated T cells are believed to cause a local expansion of infected B cells followed by spreading of the infection to other lymphocyte [84]. A subsets have been depleted by self superantigens are resistant to infections with MMTVs encoding superantigens of the same specificities as those of the self superantigens [25, 28]. Whether such a mechanism protects against infec- tions with other retroviruses than MMTV is still uncer- tain. Future findings that human retroviruses utilize su- perantigens might serve to stimulate research into new therapies based upon specific depletion of the proximal target cells. Heterologous Tran~Activation and Possible Interactions on the Posttranscriptional Level Heterologous trans-activation may occur in cells har- boring two different viruses, i.e. the transcription transcription Apparently, the human genome does not contain contain in 43]. On the other hand, a recent study reported the detection detection 54]. Further studies are needed to reveal the activities of this endogenous factor, including possible modulating effects on the nuclear export and processing of transcripts of human exogenous retroviruses. with highly they have susceptibility to with animal of human part of • • • o.. ••• • • • • • • • • •e o* • • • •• ,co a specific class 3 Baccala Tbeofilopoulos AN. gene repertoires. Hurley E, Mattson DH, Szegedy L, sequence, HRES-1, A possible autoantigen for 1 gag-reactive autoantibodies. Proc Le Tissier P, Buller RS, gene linked J Virol Buller RS, cell focus-forming (MCF) gp70 linked to virus. J Sci 1997;4:1-8 8 Buller RS, Wehrly JL, Chesebro genes conferring resistance a central nervous system disease induced a polytropic retrovirus, J Virol 9 Canivet M, Hoffman AD, Hardy Levy JA. Replication animal cells following phenotypic mixing with murine retroviruses. Virology Chakrabarti R, FM, Pandey R, Roy-Burman P. Recombination between feline exogenous endogenous re- troviral sequences generates bral endothelial cells. J Pathol 144:348- Coffin J. Structure retroviral genome. In: Varmus H, Coffin RNA Tumor Viruses, Vol. New York, Cold Spring Harbor Laboratory, 261-368; Coffin J. Endogenous viruses. In: Weiss R, Teich N, Varmus H, Coffin J, eds. Viruses, Vol. New York, Cold Spring Laboratory, 1109-1203; K, Morgan RA, Anderson WF. Safety issues related retroviral-mediated gene Gene Ther complex retroviruses. Mi- Panganiban AT. Role loendotheliosis virus envelope glycopmtein superinfection interference. J Virol 63:273- RE, Kessler Bodine D, McDon- agh K, Byrue E, Raffeld M, R, Bacher J, Zsebo Helper virus induced T cell primates after retro- viral mediated gene transfer. J Exp Med Eickbush TH. Transposing without ends: retrotransposable elements. New Biol 4:430-440;1992. DL, Arthur LO. Expression antibodies against endogenous tally transmitted macaque retroviruses primates. Virology 112:49-61;1981. Finnegan DJ. Retroviruses elements - which came first? Nature 302:105- 20 Finnegan DJ. Wandering retroviruses? Curr Biol 4:641-643; Genetic control ease in aging wild mice. Genetica 91:199-209; Kozak CA, O'Brien The Lake Casitas wild mouse: Evolving genetic resis- tance to retroviral disease. Kanagawa O. Sequence acquired immunodefi- ciency syndrome virus: Immunol 7:861-868; 24 Gitlin SD, RL, Brady molecular biology T-cell leukemia viruses. In: Cullen ruses. Oxford, Oxford University Press, 159- Golovkina TV, Chervonsky A, Dudley Ross SR. Transgenic mouse virus superantigen expression viral in- fection. Cell 69:637-645; Golovkina TV, Jaffe endogenous mouse mammary tumor vivo results viral recombination range. J Virol 68:5019-5026; Hanafusa H, Miyamoto T, Hanafusa T. A cell- associated factor essential Rous sarcoma virus. Natl Acad Sci USA 66:314-32t;1970. W, Waanders GA, Shahkov AN, Scarpet- lino L, Acha-Orbea H, MacDonald HR. Super- stimulation amplifies virus infection allows virus transmission. Cell 74:529-540; 29 Hlubinova K, Kovarik A, attempt to induce forma- antibodies against endogenous retrovi- rus BP 6 syngenic rats. Neoplasma 39:287- Hodgson CP, Chakraborty AK, Boman Retroviral vectors gene therapy genies. Curr Opin Ther Horwitz MS, Boyce-Jacino MT, Faras AJ. endogenous sequences related immunodeficiency virus type J Virol HM. Retroviral recombina- reverse transcription. Science 250: Hiigin AW, Vacchio III. A virus-encoded 'superantigen' a retrovirus- induced immunodeficiency syndrome Science 252:424-427; G, Bolognesi Htiper G. Polypeptides mammalian oncoruaviruses. Virology 63:60- Inaguma Y, T, Ikeda a truncated endogenous rine leukaemia virus, resistance gene. J Gfinzburg WH, Erfle V, Salmons viral superantigen-specific Genome 6:339-344; Jackson JB, MacDonald KL, Cadwell J, Sulli- van C, Kline WE, M, Sannerud K J, Fildes NJ, Kwok Sninsky JJ, Bowman RJ, Polesky terholm MT. Absence blood donors indeterminate Western N Engl J MS, McClure MA, D-F, Gray genes: Assignment enzymatic functions specific sequences homologies with viral enzymes. Proc Natl Aead Sci Karapetian O, Shakhov AN, Kraehenbtthl J-P, Acha-Orbea H. Retroviral infection virus model. J Exp 40 Kitagawa M, Kamisaku H, Aizawa Sado T. Bone marrow transplantation donors rescues leukemia virus- mice from leukemia: A model marrow transplantation against retro- viral infection. Leukemia 8:2200-2206; Kitagawa M, Aizawa Kamisaku H, Ikeda Sado T. Cell-free transmission resistance gene leukemia virus-induced leukemogenesis: A infection. Blood 86:1557-1563;1995. Kozak CA, Rnscetti Retroviruses in rodents. In: Levy JA, ed. Retroviridae, Vol. Press, 405-481; Krieg AM, Gourley Perl A. Endogenous retroviruses: Potential etiologic agents immunity. FASEB J 6:2537-2544; 44 Krieg AM, Gourley Steinberg AD. Heterogenous expression coordinate regulation endogenous retroviral peripheral blood Subramanyam M, Srkaly R-P. T cells virus-encoded su- su- restriction and conserved evo- lutionary features. J Exp Lal RB, DL, Coligan JE, Brodine SK, CR. Failure detect evidence T-lymphotropic virus (HTLV) type I type II in blood donors HTLV-I/II. Blood 80:544-550; Page KA, DR. Pseudo- typing with T-cell leukemia virus immunodeficiency virus host range. J Viro165:162-169;1991. Laurence J, Hodtsev tigen implicated HIV-1 repli- T cells Lee JC, JN. Autogenous virus: Reactivity several biologically distinct viruses. J Natl Limjoco TI, Dickie virus. J Linial M, Blair D. Genetics retroviruses. In: Weiss R, Teich H, Coffin J, eds. Viruses, Vot New York, Cold Laboratory, 649-783;1984. J Biomed Lock LF, E, Gilbert Jenkins NA, spontaneous germline ecotropic provirus ac- mice. EMBO J 7:4169-4177; L6wer R, Boiler K, C, Miiller-Lantzsch endogenous retrovi- ticle formation. Proc Natl Acad 54 L6wer Rev-related protein spliced transcripts the human endogenous retroviruses HTDV/HERV-K. J Ensoli B, C, DeRocco Kalyanaraman VS, Gallo RC. Expanded HIV-1 cellular tropism phenotypic mixing with endogenous re- troviruses. Science 247:848-852;1990. Choi Y, Scherer Pullen A, virus superantig- ens; two different families proteins with same functions. Rev 131:79-92; in Moloney murine leuke- a closely relat- endogenous provirus. Virology 174:135- Terry A, Tzavaras T, Cheney C, Rojko J, Neil JC. Defective endogenous pro- viruses are expressed in feline lymphoid cells: a role natural resistance group B feline leukemia viruses. J Virol Miyazawa M, Fujisawa R. Physiology endogenous routine retroviruses - gene fragments epitopes. Tohoku J Exp Mullins JI, Hoover Molecular aspects feline leukemia virus pathogenesis. In: Gallo RC, Wong-Staal eds. Retrovirus Biology York, Marcel Dekker, Ishikawa H, Takano T. Mouoclonal antibodies recognising mammalian retroviruses, lnterviro- logy 34:112-116; Nowinski RC, Kaehler virus: Widespread occurrence mice. Science 185:869-871; 63 Oldstone Molecular mimicry disease. Cell 50:81%820; DV, Bachman between feline leukemia virus subgroup B elements alters vitro biological activities viruses. J Virol Payne LN, Pani PK, Weiss RA. A epistatic gene which inhibits cellular suscepti- RSV(RAV-O). J Virol 13:455- antigenic variants troviruses. Virology Rasmussen HB, H, Clausen J. dogenous retroviruses have etiological implica- degenerative ner- vous system diseases? Acta Neurol Scand Rasmussen HB, Geny Deforges L, Tourtelotte W, Heltberg Clausen J, Expres- endogenous retroviruses onuclear cells brain tissue sclerosis patients. Multiple Sclerosis 1:82-87; Robinson HL, Astrin Senior AM, Salazar endogenous viruses: Defective, glycoprotein-expressing proviruses interfere with infections. J Virol 40:745-751; Colicelli J, between a defective retrovirus mologous sequences in host DNA: Reversion by patch repair. J Virol 53:719-726; Sheets RL, R, Klement V, Roy-Burman P. Biologically selected recombi- between feline leukemia virus (FeLV) subgroup A endogenous FeLV element. Virology 190:849-855; Sheets RL, P. Recombinant feline leukemia virus genes naturally occurring feline lympho- sarcomas. J Viro167:3118-3125;1993. Silvestris F, Williams Jr, Dammacco F. HIV-1 infection: molecular mimicry. Clin 74 Smith Endogenous retroviruses grafts (letter). N Engl J Med 328:142-143; Smith EJ. Endogenous avian leukemia viruses. ed. Avian Leukosis. Boston, Martinus NijhoffPublisbing, 101-120; Wade E, Wright DA, Koval V, Clark C, Jaquish D, Spector munodeficiency virus pseudotypes species tropism. J Viro164: Stoye J, Coffin J. Endogenous retroviruses. In: Weiss R, Teich Varmus H, Coffin J, eds. New York, Cold Laboratory, 357-404; Stuhlmann H, Berg P. Homologous recombina- copackaged retrovirus RNAs during reverse transcription. J Virol 66:2378-2388; YK, Mark WH. The endogenous ecotropic murine retroviruses producing new pro- viral insertions mouse genome. J Virol HM. Origin general nature viruses. In: Levy JA, ed. Retroviridae, Vol. York, Plenum Press, 1-18; Todaro GJ, Sherr C J, Benveniste RE. Baboons close relatives are unusual among pri- release nondefective endogenous type C viruses. Virology 72:278- DE, Reed DL, Lindell P, Kenealy WR, Winslow D, Wasel- Petteway SR Jr. Antibodies reactive immunodeficiency virus reactive only) a major enzyme-linked immunosorbent assay a blood population. J Clin Poszgay JM, Avidan SJ, Overmoyer B, Blank antigenic epitopes gene recombination in retrovirus-induced leu- immunocompetent mice. Virology Waanders GA, Shakhov AN, Held W, Karape- O, Acha-Orbea H, MacDonald HR. Pe- ripheral T cell activation deletion induced lymphocyte subsets expressing virus. J Exp Halpern MS. Avian sarcomas: pathology. In: ed. Avian Leukosis. Boston, Martin- Weiss R. Experimental biology viruses. In: Weiss R, Teich N, Var- H, Coffin J, eds. Tumor Viruses, New York, Cold Spring Harbor Labora- tory, 209-260;1985. Mager DL, Leong JC. Endoge- retroviruses. In: Levy JA, ed. Retroviridae, Vol. New York, Plenum Press, Williams LM, Cloyd MW. Polymorphic hu- gene(s) determines differential suscepti- CD4 lymphocytes infection by cer- isolates. Virology 184:723-728; Viral pseudotypes mixing. Arch Viro150:I-15;1976. J Biomed Sci 1997;4:1-8