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Potential human health risks associated with animal retroviruses: Some hypotheses
Medical Hypotheses (1989) 29, 195-198 0 Longman Group UK Ltd 1989
Potential Human Health Risks Associated with Animal Retroviruses: Some Hypotheses G. DI GUARD0 Viale Pasteur, 77 -
00144 -
E.U.R., Rome, Italy.
Abstract - Several studies have demonstrated the existence of morphological, biological, genetic and antigenic correlations between human and animal retroviruses. Furthermore, some agents of bovine and feline origin can also be considered useful comparative models for the pathogenetic study of human diseases such as leukaemia, acquired immunodeficiency syndrome (AIDS) and multiple sclerosis (MS). In spite of the existence of data suggesting a possible role of some animal retroviruses (e.g. the bovine leukosis virus, BLV) in the etiology and epidemiology of human leukaemia and MS, the true zoonotic potential of such agents remains unknown, but their genetic and antigenic linkages with some human lentiviruses (such as the human immunodeficiency virus-l, HIV1) can make them hypothetically responsible for a certain number of false-positive serological reactions in man, especially in those subjects who are professionally exposed to animal lentiviruses. In the present paper particular reference is made to this last hypothesis which, if confirmed, would suggest a larger scale-utilization of more specific diagnostic tests for HIV infection in man, such as the immunoblotting techniques.
Introduction
Several animal lentiviruses have recently been proven to share a number of morphological, biological, genetic and antigenic features in common with the viral agent responsible for acquired immunodeficiency syndrome (AIDS) in man, which is now named human immunodeficiency virus-l (HIV-l) (1). Such agents include the Maedi-Visna virus (MVV) (2), the caprine arthritis-encephalitis virus (CAEV) (3), the equine infectious anemia virus (EIAV) (4) and, most recently, the so-called “bovine immunodeficiency-like virus” (BIV) (5), a Visna-like
syncytia-producing agent isolated from cattle with persistent lymphocytosis (6, 7, S), and the “feline T-lymphotropic lentivirus” (FTLV), which seems, however, to be more closely related to HIV-l in terms of morphology and disease pathogenesis (9). Furthermore, the multifocal granulomatous encephalitis which is induced by HIV-l in adult and pediatric patients (10, 11, 12, 13) and by the simian T-lymphotropic virus type III (STLV-III), or simian immunodeficiency virus-l (SW-l) in monkeys (14, 15, 16, 17), closely resembles that occurring in MVV-infected sheep and CAEV-
195 MH
C
196 infected goats, with the only difference that these latter are more demyelinating (18). Reliable serological tests, such as ELISA, are currently utilized in epidemiological surveys investigating the prevalence of specific antibodies to HIV-l and -2 in groups of human population at risk for AIDS (19, 20), but no evidence has been provided until now that all seropositive reactions of this type are exclusively associated with antigenic stimulation by HIV and not hypothetically, at least in a certain percentage of cases, with antigenic stimulation by MVV, CAEV, EIAV or BIV, especially in those patients exposed for professional or other reasons to prolonged contacts with animals infected by such lentiviruses (21). With regard to the possible health hazards arising from human exposure and/or contact with animal retroviruses, no definitive answer has been given until now about the true zoonotic potential of such agents, if any. However, it is worthy to be mentioned here that infection of human fibroblastoid cell cultures derived from leukaemic bone marrow has been successfully obtained with the recently characterized BIV (22), which was previously named bovine Visna-like virus (BVV) (7, 8). On the other hand, close morphological, genetic and antigenic similarities have been observed between human and animal oncoviruses, as in the case of the human T-cell lymphotropic virus types I and II (HTLV-I and -11, respectively) and the bovine leukosis for leukaemia) virus (BLV) (23, 24), while epidemiological linkages have been established between BLV-infected cattle herds and human leukaemia (25). Furthermore, strong geographic correlations have been documented between production and consumption of dairy products and multiple sclerosis (MS) (26), leading to the hypothesis that BLV could be transmitted in such foodstuffs and cause disease in humans (24). Finally, presence of serum antibodies cross-reacting with HTLV-I, -11 and -111 and in-situ hybridization of RNA from cerebrospinal fluid cells with HTLV-I have been reported in patients suffering from MS (27), leading also in this case to the hypothesis that the “fingerprints” found might be actually those of BLV (24), which is closely correlated - as already mentioned - with HTLV-I from both genetic and antigenic point of view (23).
MEDICAL HYPOTHESES
Conclusions
On the basis of what above, in spite of the existence of works (28,29) disputing some of the data reported here (see reference 27), suffice it to say that full attention should be paid to the problem of exactly defining the real health hazards, if any, arising from human exposure and/or contact with animal retroviruses. In this direction, extensive research should be carried out on so-called “risk categories”, such as farmers, veterinarians, laboratory technicians, etc. ; as a consequence, a tight cooperation between human and animal health services would also be required to achieve this objective. Among others, a continuous exchange of bilateral informations between these two sectors would certainly help better understand the pathogenesis of some human retroviral infections such as those caused by HIV-l and -2, for which both the recently characterized BIV (5) and identified FTLV (9) can be considered useful comparative and speculative models. On the other hand, it is my opinion that this same form of cooperation will also be of great help in defining the true role of some HIV-lgenetically and antigenically related animal lentiviruses (MVV, CAEV, EIAV, BIV) as possible causative agents of false-positive serological reactions to HIV-l in man, especially in those subjects exposed for professional or other reasons to prolonged contacts with animals infected by such viruses (21). In this regard, though HIV-l differs considerably from animal lentiviruses in: a) its close association with the Td antigen, which is an essential part of the virus receptor on the T-cell surface (3, 30, 31), b) the pathogenetic behaviour of the infection, which is usually characterized by minimal or selective impairment of the immune system in animal lentiviroses (3), it should be firmely kept in mind that the identification of HIV-l as the viral agent responsible for human AIDS and other related syndromes (lymphadenopathy syndrome, LAS; AIDS-related complex, ARC; pre-AIDS) has recently occurred (32, 33, 34). Consequently, there are still important details and peculiarities of this infection that need further clarification. Among these, the possibility of obtaining false-positive serological reactions to HIV-l in man due to previous exposure and/or contact with HIV-l-genetically and antigenically related animal lentiviruses should be thoroughly investigated (21).
POTENTIAL HUMAN HEALTH RISKS ASSOCIATED
WITH ANIMAL RETROVIRUSES
Finally, though just hypothetical, this assumption would suggest a larger scale-utilization of the most recently developed diagnostic tests and kits for HIV and other infections in man and animals (21, 35), such as Western Blotting, Immunoblotting, Dot Blotting (36) and monoclonal antibodies (39, also in consideration of the fact that recent comparative investigations between ELISA and immunoblotting techniques (20) have shown that only these latter are able to distinguish, in B vey precise way, serological responses due to antigenically related lentiviruses, as in the case, for instance, of HIV-l and HIV-2 infected patients. References M, Read-Connole E, Gartner S. Biological 1. Popovic properties of HTLV-III/LAV: A possible pathway of natural infection in vivo. Ann. Inst. Pasteur/Immunol. 137D: 413, 1986. F, Gallo R C, et al. Sequence 2. Gonda M A. Wong-Staal homology and morphologic similarity of HTLV-III and visna virus, a pathogenic lentivirus. Science 227: 173, 1985. of lentivirus infections. Nature 3. Haase A T. Pathogenesis (London) 322: 130, 1986. 4. Stephens R M, Casey J W, Rice N R. Equine infectious anemia virus gag and pol genes: relatedness to visna and AIDS virus. Science 231: 589, 1986. 5. Gonda M A, Braun M J, Carter S G, et al. Characterization and molecular cloning of a bovine lentivirus related to human immunodeficiency virus. Nature (London) 330: 388, 1987. 6. Coward J E, Harter D H, Morgan C. Electron microscopic observation of visna virus-infected cell cultures. VirOlogy 40: 1030, 1970. 7. Van Der Maaten M J. Boothe A D. Seeer C L. Isolation of a virus from cattle with persistent Tymphocytosis. J. Natl. Cancer Inst. 49: 1649. 1972. A D. Van Der Maaten M J. Ultrastructural 8. Boothe studies of a visna-like syncytia-producing virus from cattle with lymphocytosis. J. Virol. 13: 197, 1974. N C, Ho E W, Brown M L, Yamamoto J K. 9. Pedersen Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency-like syndrome. Science 235: 790, 1987. L G, Sharer L R, Cho E-S, et al. HTLV10. Epstein IIl/LAV-like retrovirus particles in the brains of patients wiih AIDS encephalopathy. AIDS Res. 1: 447, i985. 11. Ho D D, Rota T R, Schoolev R T. et al. Isolation of HTLV-III from cerebrospinal kuid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N. Engl. J. Med. 313: 1493. 1985. giant 12. Sharer L R, Cho E-S, Epstein L G. Multinucleated cells and HTLV-III in AIDS encephalopathy. Hum. Pathol. 16: 760. 1985. of 13 Sharer L R. Epstein L G. Cho E-S, et al. Pathology AIDS encephalopathy in children: evidence for LAV/HTLV-III , infection of brain. Hum. Pathol. 17: 271. 1986.
197
14. Daniel M D, Letvin N L, King N W, et al. Isolation of T-cell tropic HTLV-III like retrovirus from macaques. Science 228: 1201, 1985. 15. Kanki P J, McLane M F, King N W, et al. Serological identification and characterization of a macaque Tlymphotropic retrovirus closely related to HTLV-III. Science 228: 1199, 1985. M, Yetz J M, Letvin N L. In vitro growth 16. Kannagi characteristics of simian T-lymphotropic virus type III. Proc. Natl. Acad. Sci. USA 82: 7053. 1985. 17. Letvin N L, Daniel M D, Sehaal P K, et al. Induction of AIDS-like disease in macaques with T-cell tropic retrovirus STLV-III. Science 230: 71. 1985. 18. King N W. Simian models of acquired immunodeficiency syndrome (AIDS): A review. Vet. Pathol. 23: 345, 1986. 19. De Majo E, Ravina A, Ricciarelli L, et al. Screening and confirmatory tests for antibody to HTLV-III/LAV retrovirus in individuals at risk for AIDS. La Ricerca Clin. Lab. 16: 489, 1986. D. Sierologia per HIV-1 e HIV-2 in 20. Vinci E, Fumarola un gruppo di tossicodipendenti. Proceedings of AIPaC 37th National Congress, June. 3-6. 1987, Rome, Italy, P. 207. G. Vulcan0 G. Serological identification of 21. Di Guard0 HIV-infected human patients: An original hypothesis (correspondence). N. Engl. J. Med. 318: 18, 1988. J A. Billiau A, Vanderschueren B. Infection 22. Georgiades of human cell cultures with bovine visna virus. J. Gen. Viral. 38: 375, 1978. J G, Kettman R, et al. Tram 23. Rosen C A. Sodroski activation of the bovine leukemia virus long terminal repeat in BLV-infected cells. Science 227: 320, 1985. 24. Cunningham A S. Bovine leukaemia virus and multiple sclerosis (correspondence). Nature (London) 320: 219, 1986. 25. Donham K J, Berg J W, Sawin R S. Epidemiologic relationships of the bovine population and human leukemia in Iowa. Am. J. Epidem. 112: 80. 1980. 26. Agranoff B W, Goldberg D. Diet and the geographical distribution of multiple sclerosis. Lancet ii: 1061, 1974. 27. Koprowski H, DeFreitas E C, Harper M E. et al. Multiple sclerosis and human T-cell lymphotropic retroviruses. Nature (London) 318: 154, 1985. C, Burks J S, et al. Analysis of 28. Hauser S L, Aubert human T-lymphotropic virus sequences in multiple sclerosis tissue. Nature (London) 322: 176, 1986. 29. Karpas A, Kgmpf U, Siden A, et al. Lack of evidence for involvement bf known human retroviruses in multiple sclerosis. Nature (London) 322: 177. 1986. 30. Dalgleish A G. Beverly P’C L, Clapham P R, et al. The CO4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature (London) 312: 763, 1984. 31. Klatzmann D. Champagne E, Chamaret S. et al. Tlymphocyte T4 molecule behaves as i‘ receptor for human retrovirus LAV. Nature (London) 312: 767. 1984. 32. Barr&Sinoussi F, Chermann J C, Rey F. et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immunodeficiency syndrome (AIDS). Science 220: 868, 1983. 33. Popovic M, Sarngadharan M G. Read E, Gallo R C. Detection. isolation and continues production of cvtopathic human T-lymphotropic retroiiruses (HTLV-\II) from patients with AIDS and ore-AIDS. Science 224: 497. 1984. M G, Popovic M, Bruch L, et al. Anti34 Sarngadharan
198 bodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS. Science 224: 506, 1984. 35 . Di Guard0 G, Ansuini A. Modern diagnostic and prophylactic methods applicable to intensive animal husbandry. Proceedings of 12th Conference of the OIE
MEDICAL
HYPOTHESES
Regional Commission for Europe, Berlin (GDR), September. 16-19. 1986, P. 215. 36. Aiuti F, Carini C, Luzi G. Diagnosi sierologica ed immunologica delle infezioni da HIV. Proceedings of AIPaC 37th National Congress, Rome, Italy, June. 3-6. 1987. P. 101.
Potential Human Health Risks Associated with Animal Retroviruses: Some Hypotheses G. DI GUARD0 Viale Pasteur, 77 -
00144 -
E.U.R., Rome, Italy.
Abstract - Several studies have demonstrated the existence of morphological, biological, genetic and antigenic correlations between human and animal retroviruses. Furthermore, some agents of bovine and feline origin can also be considered useful comparative models for the pathogenetic study of human diseases such as leukaemia, acquired immunodeficiency syndrome (AIDS) and multiple sclerosis (MS). In spite of the existence of data suggesting a possible role of some animal retroviruses (e.g. the bovine leukosis virus, BLV) in the etiology and epidemiology of human leukaemia and MS, the true zoonotic potential of such agents remains unknown, but their genetic and antigenic linkages with some human lentiviruses (such as the human immunodeficiency virus-l, HIV1) can make them hypothetically responsible for a certain number of false-positive serological reactions in man, especially in those subjects who are professionally exposed to animal lentiviruses. In the present paper particular reference is made to this last hypothesis which, if confirmed, would suggest a larger scale-utilization of more specific diagnostic tests for HIV infection in man, such as the immunoblotting techniques.
Introduction
Several animal lentiviruses have recently been proven to share a number of morphological, biological, genetic and antigenic features in common with the viral agent responsible for acquired immunodeficiency syndrome (AIDS) in man, which is now named human immunodeficiency virus-l (HIV-l) (1). Such agents include the Maedi-Visna virus (MVV) (2), the caprine arthritis-encephalitis virus (CAEV) (3), the equine infectious anemia virus (EIAV) (4) and, most recently, the so-called “bovine immunodeficiency-like virus” (BIV) (5), a Visna-like
syncytia-producing agent isolated from cattle with persistent lymphocytosis (6, 7, S), and the “feline T-lymphotropic lentivirus” (FTLV), which seems, however, to be more closely related to HIV-l in terms of morphology and disease pathogenesis (9). Furthermore, the multifocal granulomatous encephalitis which is induced by HIV-l in adult and pediatric patients (10, 11, 12, 13) and by the simian T-lymphotropic virus type III (STLV-III), or simian immunodeficiency virus-l (SW-l) in monkeys (14, 15, 16, 17), closely resembles that occurring in MVV-infected sheep and CAEV-
195 MH
C
196 infected goats, with the only difference that these latter are more demyelinating (18). Reliable serological tests, such as ELISA, are currently utilized in epidemiological surveys investigating the prevalence of specific antibodies to HIV-l and -2 in groups of human population at risk for AIDS (19, 20), but no evidence has been provided until now that all seropositive reactions of this type are exclusively associated with antigenic stimulation by HIV and not hypothetically, at least in a certain percentage of cases, with antigenic stimulation by MVV, CAEV, EIAV or BIV, especially in those patients exposed for professional or other reasons to prolonged contacts with animals infected by such lentiviruses (21). With regard to the possible health hazards arising from human exposure and/or contact with animal retroviruses, no definitive answer has been given until now about the true zoonotic potential of such agents, if any. However, it is worthy to be mentioned here that infection of human fibroblastoid cell cultures derived from leukaemic bone marrow has been successfully obtained with the recently characterized BIV (22), which was previously named bovine Visna-like virus (BVV) (7, 8). On the other hand, close morphological, genetic and antigenic similarities have been observed between human and animal oncoviruses, as in the case of the human T-cell lymphotropic virus types I and II (HTLV-I and -11, respectively) and the bovine leukosis for leukaemia) virus (BLV) (23, 24), while epidemiological linkages have been established between BLV-infected cattle herds and human leukaemia (25). Furthermore, strong geographic correlations have been documented between production and consumption of dairy products and multiple sclerosis (MS) (26), leading to the hypothesis that BLV could be transmitted in such foodstuffs and cause disease in humans (24). Finally, presence of serum antibodies cross-reacting with HTLV-I, -11 and -111 and in-situ hybridization of RNA from cerebrospinal fluid cells with HTLV-I have been reported in patients suffering from MS (27), leading also in this case to the hypothesis that the “fingerprints” found might be actually those of BLV (24), which is closely correlated - as already mentioned - with HTLV-I from both genetic and antigenic point of view (23).
MEDICAL HYPOTHESES
Conclusions
On the basis of what above, in spite of the existence of works (28,29) disputing some of the data reported here (see reference 27), suffice it to say that full attention should be paid to the problem of exactly defining the real health hazards, if any, arising from human exposure and/or contact with animal retroviruses. In this direction, extensive research should be carried out on so-called “risk categories”, such as farmers, veterinarians, laboratory technicians, etc. ; as a consequence, a tight cooperation between human and animal health services would also be required to achieve this objective. Among others, a continuous exchange of bilateral informations between these two sectors would certainly help better understand the pathogenesis of some human retroviral infections such as those caused by HIV-l and -2, for which both the recently characterized BIV (5) and identified FTLV (9) can be considered useful comparative and speculative models. On the other hand, it is my opinion that this same form of cooperation will also be of great help in defining the true role of some HIV-lgenetically and antigenically related animal lentiviruses (MVV, CAEV, EIAV, BIV) as possible causative agents of false-positive serological reactions to HIV-l in man, especially in those subjects exposed for professional or other reasons to prolonged contacts with animals infected by such viruses (21). In this regard, though HIV-l differs considerably from animal lentiviruses in: a) its close association with the Td antigen, which is an essential part of the virus receptor on the T-cell surface (3, 30, 31), b) the pathogenetic behaviour of the infection, which is usually characterized by minimal or selective impairment of the immune system in animal lentiviroses (3), it should be firmely kept in mind that the identification of HIV-l as the viral agent responsible for human AIDS and other related syndromes (lymphadenopathy syndrome, LAS; AIDS-related complex, ARC; pre-AIDS) has recently occurred (32, 33, 34). Consequently, there are still important details and peculiarities of this infection that need further clarification. Among these, the possibility of obtaining false-positive serological reactions to HIV-l in man due to previous exposure and/or contact with HIV-l-genetically and antigenically related animal lentiviruses should be thoroughly investigated (21).
POTENTIAL HUMAN HEALTH RISKS ASSOCIATED
WITH ANIMAL RETROVIRUSES
Finally, though just hypothetical, this assumption would suggest a larger scale-utilization of the most recently developed diagnostic tests and kits for HIV and other infections in man and animals (21, 35), such as Western Blotting, Immunoblotting, Dot Blotting (36) and monoclonal antibodies (39, also in consideration of the fact that recent comparative investigations between ELISA and immunoblotting techniques (20) have shown that only these latter are able to distinguish, in B vey precise way, serological responses due to antigenically related lentiviruses, as in the case, for instance, of HIV-l and HIV-2 infected patients. References M, Read-Connole E, Gartner S. Biological 1. Popovic properties of HTLV-III/LAV: A possible pathway of natural infection in vivo. Ann. Inst. Pasteur/Immunol. 137D: 413, 1986. F, Gallo R C, et al. Sequence 2. Gonda M A. Wong-Staal homology and morphologic similarity of HTLV-III and visna virus, a pathogenic lentivirus. Science 227: 173, 1985. of lentivirus infections. Nature 3. Haase A T. Pathogenesis (London) 322: 130, 1986. 4. Stephens R M, Casey J W, Rice N R. Equine infectious anemia virus gag and pol genes: relatedness to visna and AIDS virus. Science 231: 589, 1986. 5. Gonda M A, Braun M J, Carter S G, et al. Characterization and molecular cloning of a bovine lentivirus related to human immunodeficiency virus. Nature (London) 330: 388, 1987. 6. Coward J E, Harter D H, Morgan C. Electron microscopic observation of visna virus-infected cell cultures. VirOlogy 40: 1030, 1970. 7. Van Der Maaten M J. Boothe A D. Seeer C L. Isolation of a virus from cattle with persistent Tymphocytosis. J. Natl. Cancer Inst. 49: 1649. 1972. A D. Van Der Maaten M J. Ultrastructural 8. Boothe studies of a visna-like syncytia-producing virus from cattle with lymphocytosis. J. Virol. 13: 197, 1974. N C, Ho E W, Brown M L, Yamamoto J K. 9. Pedersen Isolation of a T-lymphotropic virus from domestic cats with an immunodeficiency-like syndrome. Science 235: 790, 1987. L G, Sharer L R, Cho E-S, et al. HTLV10. Epstein IIl/LAV-like retrovirus particles in the brains of patients wiih AIDS encephalopathy. AIDS Res. 1: 447, i985. 11. Ho D D, Rota T R, Schoolev R T. et al. Isolation of HTLV-III from cerebrospinal kuid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N. Engl. J. Med. 313: 1493. 1985. giant 12. Sharer L R, Cho E-S, Epstein L G. Multinucleated cells and HTLV-III in AIDS encephalopathy. Hum. Pathol. 16: 760. 1985. of 13 Sharer L R. Epstein L G. Cho E-S, et al. Pathology AIDS encephalopathy in children: evidence for LAV/HTLV-III , infection of brain. Hum. Pathol. 17: 271. 1986.
197
14. Daniel M D, Letvin N L, King N W, et al. Isolation of T-cell tropic HTLV-III like retrovirus from macaques. Science 228: 1201, 1985. 15. Kanki P J, McLane M F, King N W, et al. Serological identification and characterization of a macaque Tlymphotropic retrovirus closely related to HTLV-III. Science 228: 1199, 1985. M, Yetz J M, Letvin N L. In vitro growth 16. Kannagi characteristics of simian T-lymphotropic virus type III. Proc. Natl. Acad. Sci. USA 82: 7053. 1985. 17. Letvin N L, Daniel M D, Sehaal P K, et al. Induction of AIDS-like disease in macaques with T-cell tropic retrovirus STLV-III. Science 230: 71. 1985. 18. King N W. Simian models of acquired immunodeficiency syndrome (AIDS): A review. Vet. Pathol. 23: 345, 1986. 19. De Majo E, Ravina A, Ricciarelli L, et al. Screening and confirmatory tests for antibody to HTLV-III/LAV retrovirus in individuals at risk for AIDS. La Ricerca Clin. Lab. 16: 489, 1986. D. Sierologia per HIV-1 e HIV-2 in 20. Vinci E, Fumarola un gruppo di tossicodipendenti. Proceedings of AIPaC 37th National Congress, June. 3-6. 1987, Rome, Italy, P. 207. G. Vulcan0 G. Serological identification of 21. Di Guard0 HIV-infected human patients: An original hypothesis (correspondence). N. Engl. J. Med. 318: 18, 1988. J A. Billiau A, Vanderschueren B. Infection 22. Georgiades of human cell cultures with bovine visna virus. J. Gen. Viral. 38: 375, 1978. J G, Kettman R, et al. Tram 23. Rosen C A. Sodroski activation of the bovine leukemia virus long terminal repeat in BLV-infected cells. Science 227: 320, 1985. 24. Cunningham A S. Bovine leukaemia virus and multiple sclerosis (correspondence). Nature (London) 320: 219, 1986. 25. Donham K J, Berg J W, Sawin R S. Epidemiologic relationships of the bovine population and human leukemia in Iowa. Am. J. Epidem. 112: 80. 1980. 26. Agranoff B W, Goldberg D. Diet and the geographical distribution of multiple sclerosis. Lancet ii: 1061, 1974. 27. Koprowski H, DeFreitas E C, Harper M E. et al. Multiple sclerosis and human T-cell lymphotropic retroviruses. Nature (London) 318: 154, 1985. C, Burks J S, et al. Analysis of 28. Hauser S L, Aubert human T-lymphotropic virus sequences in multiple sclerosis tissue. Nature (London) 322: 176, 1986. 29. Karpas A, Kgmpf U, Siden A, et al. Lack of evidence for involvement bf known human retroviruses in multiple sclerosis. Nature (London) 322: 177. 1986. 30. Dalgleish A G. Beverly P’C L, Clapham P R, et al. The CO4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature (London) 312: 763, 1984. 31. Klatzmann D. Champagne E, Chamaret S. et al. Tlymphocyte T4 molecule behaves as i‘ receptor for human retrovirus LAV. Nature (London) 312: 767. 1984. 32. Barr&Sinoussi F, Chermann J C, Rey F. et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immunodeficiency syndrome (AIDS). Science 220: 868, 1983. 33. Popovic M, Sarngadharan M G. Read E, Gallo R C. Detection. isolation and continues production of cvtopathic human T-lymphotropic retroiiruses (HTLV-\II) from patients with AIDS and ore-AIDS. Science 224: 497. 1984. M G, Popovic M, Bruch L, et al. Anti34 Sarngadharan
198 bodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS. Science 224: 506, 1984. 35 . Di Guard0 G, Ansuini A. Modern diagnostic and prophylactic methods applicable to intensive animal husbandry. Proceedings of 12th Conference of the OIE
MEDICAL
HYPOTHESES
Regional Commission for Europe, Berlin (GDR), September. 16-19. 1986, P. 215. 36. Aiuti F, Carini C, Luzi G. Diagnosi sierologica ed immunologica delle infezioni da HIV. Proceedings of AIPaC 37th National Congress, Rome, Italy, June. 3-6. 1987. P. 101.