RESUMEN
Between late December 1999 and late April 2000, three locally bred Friesian calves (ageing 25, 28 and 35 days) in a dairy farm, at Al-Ahsa locality of the eastern region of Saudi Arabia showed dullness and inappetence. Their rectal temperatures ranged between 41 and 41.5 degrees C. One to 2 days later and onwards, the calves showed lacrimation, nasal discharge, salivation, oedema of the head, conjunctivitis, exo-ophthalmia and corneal opacity. One calf showed diarrhoea. The superficial lymph nodes were oedematous and swollen. The calves died after 7, 5 and 8 days, respectively, following the onset of the disease. Calves and rabbits were experimentally infected with materials from the naturally infected calves. The rabbits showed fever, mild conjunctivitis and one rabbit showed wet faeces. The experimentally inoculated calves showed rise in temperature and mild symptoms but none of them died. The virus from the naturally infected calves and from the experimentally infected rabbits was identified as malignant catarrhal fever (MCF) virus using both the complement fixation test and the fluorescent antibody test, employing a reference anti-serum against the WC 11 strain of MCF virus. Serological survey for MCF antibodies in cattle, sheep and goats from the affected farm revealed that 54% of the examined animals were positive. The situation of MCF in Saudi Arabia was discussed in relation to sheep and wild game. This paper constitutes the first report of MCF in Saudi Arabia and the Gulf region.
Asunto(s)
Anticuerpos Antivirales/sangre , Herpesviridae/inmunología , Fiebre Catarral Maligna/epidemiología , Virus Inductores de Focos en Células del Visón/inmunología , Animales , Animales Recién Nacidos , Bovinos , Pruebas de Fijación del Complemento/veterinaria , Técnica del Anticuerpo Fluorescente/veterinaria , Cabras , Herpesviridae/aislamiento & purificación , Fiebre Catarral Maligna/etiología , Fiebre Catarral Maligna/patología , Virus Inductores de Focos en Células del Visón/aislamiento & purificación , Conejos , Arabia Saudita/epidemiología , OvinosRESUMEN
In a previous study we identified the subpopulations of thymus cells that were infected by the lymphomagenic MCF13 murine leukemia virus (MLV) (F. K. Yoshimura, T. Wang, and M. Cankovic, J. Virol. 73:4890-4898, 1999) and observed an effect on thymus size by virus infection. In this report we describe our results which demonstrate that MCF13 MLV infection of thymuses reduced the number of T lymphocytes in this organ. Histological examination showed diffuse lymphocyte depletion, which was most striking in the CD4(+) CD8(+) lymphocyte-enriched cortical zone. Consistent with this, flow cytometric analysis showed that the lymphocytes which were depleted were predominantly the immature CD3(-) CD4(+) CD8(+) and CD3(+) CD4(+) CD8(+) cells. A comparison of the percentages of live, apoptotic, and dead cells of the gp70(+) and gp70(-) thymic lymphocytes suggested that this effect on thymus cellularity is a result of virus infection. Studies of the survival of thymic T lymphocytes in culture showed that cells from MCF13 MLV-inoculated mice underwent greater apoptosis and death than cells from control animals. Assays for apoptosis included 7-amino-actinomycin D staining, DNA fragmentation, and cleavage of caspase-3 and poly(ADP-ribose) polymerase proenzymes. Our results suggest that apoptosis of thymic lymphocytes by virus infection is an important step in the early stages of MCF13 MLV tumorigenesis.
Asunto(s)
Apoptosis , Leucemia Experimental/patología , Virus Inductores de Focos en Células del Visón/inmunología , Infecciones por Retroviridae/patología , Linfocitos T/virología , Infecciones Tumorales por Virus/patología , Animales , Linfocitos T CD4-Positivos/patología , Linfocitos T CD4-Positivos/virología , Linfocitos T CD8-positivos/patología , Linfocitos T CD8-positivos/virología , Caspasa 3 , Caspasas/metabolismo , Células Cultivadas , Fragmentación del ADN , Precursores Enzimáticos/metabolismo , Citometría de Flujo , Leucemia Experimental/inmunología , Leucemia Experimental/virología , Ratones , Ratones Endogámicos AKR , Poli(ADP-Ribosa) Polimerasas/metabolismo , Infecciones por Retroviridae/inmunología , Infecciones por Retroviridae/virología , Linfocitos T/patología , Timo/patología , Timo/virología , Infecciones Tumorales por Virus/inmunología , Infecciones Tumorales por Virus/virologíaRESUMEN
The Asian mouse Mus castaneus is resistant to infection by the polytropic mink cell focus-inducing (MCF) subgroup of murine leukemia viruses (MuLVs). Genetic crosses showed this recessive resistance to be governed by a single gene that maps at or near the gene encoding the polytropic viral receptor, Rmc1. To investigate this resistance, we mated M. castaneus with mice carrying the wild mouse Sxv variant of the Rmc1 receptor that allows infection by xenotropic as well as polytropic virus. Unlike other F1 hybrids of M. castaneus, these F1 mice were resistant to both xenotropic and polytropic classes of MuLVs. Analysis of backcrossed progeny of the F1 hybrids mated to Sxv mice indicates that resistance is due to inheritance of two M. castaneus genes. Cells from individual backcross mice were also examined for cell surface antigen by fluorescence-activated cell sorter analysis with monoclonal antibodies reactive with xenotropic or MCF virus env glycoproteins. A correlation was observed between virus resistance and antigen, suggesting that virus resistance is due to expression of endogenous viral envelope genes that interfere with infection by exogenous virus. Since the inbred strain Rmc1 receptor remains functional in the presence of these M. castaneus genes, and since M. castaneus contains multiple copies of xenotropic MuLV env genes, we suggest that these resistance genes control expression of xenotropic env glycoprotein that interferes with exogenous virus in cells containing the Sxv variant of Rmc1.
Asunto(s)
Proteínas de la Membrana , Virus Inductores de Focos en Células del Visón/inmunología , Muridae/inmunología , Receptores Virales/metabolismo , Animales , Células Cultivadas , Femenino , Inmunidad Innata , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos DBA , Virus Inductores de Focos en Células del Visón/metabolismo , Muridae/genética , Receptores Acoplados a Proteínas G , Receptores Virales/genética , Proteínas del Envoltorio Viral/inmunología , Receptor de Retrovirus Xenotrópico y PolitrópicoRESUMEN
Prevention of high frequency spontaneous T cell lymphoma development in AKR mice by mAb 18-5 treatment was shown to involve inhibition of the recombinant Class I MCF virus formation and elimination of the early occurring potential lymphoma cells (PLCs). A low B cell lymphoma incidence (16% at a mean latency of 540 days) and a low level of PLCs (yielding 12% B cell lymphoma development following lymphoid cell transfer) was observed in mAb 18-5 treated mice (in contrast to a high PLC level in thymectomized AKR mice that could be experimentally triggered to progress to overt CD5+ B cell lymphomas). Administration of anti CD8 mAb or IL-4 to 12-month-old mAb 18-5 pre-treated mice only slightly increased B cell lymphoma incidence (up to 30-40%). Exposure to split-dose irradiation resulted in 26% B cell lymphomas at a 250 day mean latency. The phenotypes of the B lymphomas developing in mAb 18-5 treated mice were: B220+ (14.8+, 6B2+), 6C3+, Mac2+, CD5-. Most lymphomas expressed l-a and surface IgM, pointing to their mature B cell characteristics. Moreover, in some of the lymphomas, high levels of IgM production and secretion were determined. A comparison of the morphological characteristics (based on light and ultrastructure microscopy) of CD5+ and CD5- B cell lymphomas developing in AKR mice indicated marked differences. Analysis of the IgH locus of representative CD5- B lymphomas showed an identical pattern of IgH rearrangement in some tumors (similar to previous findings among CD5+ lymphomas). The virological analysis of the CD5- B cell lymphomas (similar to those observed in the CD5+ B cell lymphomas of AKR origin) showed that their development did not require formation of the pathogenic MCF recombinant viruses. The differences observed between the CD5+ and CD5- B cell lymphomas developing in AKR mice (following prevention of spontaneous T cell lymphomagenesis) may be due to their origin of different B cell precursors or from B cells at different levels of differentiation.
Asunto(s)
Linfoma de Células B/etiología , Ratones Endogámicos AKR/inmunología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Antígenos CD5/análisis , ADN Viral/análisis , Reordenamiento Génico de Cadena Pesada de Linfocito B , Genes de Inmunoglobulinas , Inmunización Pasiva , Inmunoglobulinas/biosíntesis , Inmunofenotipificación , Linfoma de Células B/inmunología , Ratones , Virus Inductores de Focos en Células del Visón/inmunología , Infecciones Tumorales por Virus/prevención & controlRESUMEN
Incubation of murine spleen cells with antisense oligonucleotide complementary to initiation site of this gene highly increased RNA synthesis relative to the normal T- and B-lymphocytes from spleen. In macrophages, inhibition of gene env expression stimulated phagocytosis and IL-1 production. Under these conditions, the level of expression of proviral envelope transmembrane p15E protein, which in infectious type C retroviruses is known to be immunosuppressive, decreased in spleen cells. Antisense oligonucleotide stimulatory effect on murine spleen cell RNA synthesis is presumably related to the reduced production of endogenous p15E.
Asunto(s)
Linfocitos B/inmunología , Genes env , Macrófagos/inmunología , Virus Inductores de Focos en Células del Visón/genética , Linfocitos T/inmunología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Células Cultivadas , Interleucina-1/biosíntesis , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Virus Inductores de Focos en Células del Visón/inmunología , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos , Fagocitosis/genética , ARN Viral/biosíntesis , Bazo/citología , Bazo/inmunologíaRESUMEN
In earlier studies, we have shown that superinfection of an interleukin-2 (IL-2)-dependent, Moloney murine leukemia virus (MoMuLV)-induced rat T-cell lymphoma line (4437A) with mink cell focus-forming (also called polytropic) murine retroviruses induces rapid progression to IL-2-independent growth. In this report, we present evidence that the vast majority (> 90%) of the IL-2-independent lines established from polytropic or xenotropic virus-infected 4437A cells carry provirus insertions in the 3' untranslated region of the IL-9 receptor gene (Gfi-2 [for growth factor independence-2]/IL-9R). Prior to superinfection, the cells express neither IL-9 nor IL-9R. Following superinfection and provirus insertion in the Gfi-2/IL-9R locus, the cells express high levels of mRNA transcripts with a truncated 3' untranslated region which are predicted to encode the normal IL-9R protein product. The same IL-2-independent cells also express IL-9 which is induced by an insertional mutagenesis-independent mechanism. The establishment of an IL-9-dependent autocrine loop was sufficient to render the cells IL-2 independent, as suggested by the finding that 4437A cells, expressing a stably transfected Gfi-2/IL-9R construct, do not require IL-2 when maintained in IL-9-containing media. Additional experiments designed on the basis of these results showed that IL-9 gene expression is induced rapidly following the infection of 4437A cells by polytropic or xenotropic viruses and occurs in the absence of selection for IL-2-independent growth. Taken together, these data suggest that infection of 4437A cells by mink cell focus-forming or xenotropic viruses induces the expression of IL-9, which in turn rapidly selects the cells expressing the IL-9 receptor through an insertional mutagenesis-dependent mechanism. Given that both the polytropic and xenotropic viruses can induce the IL-9-dependent autocrine loop, the reduced ability of the xenotropic viruses to rapidly induce IL-2 independence in culture and tumors in animals is likely to be the result of their lower growth rates.
Asunto(s)
Expresión Génica , Interleucina-2/farmacología , Interleucina-2/fisiología , Virus Inductores de Focos en Células del Visón/inmunología , Virus de la Leucemia Murina de Moloney/inmunología , Receptores de Interleucina-2/fisiología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Línea Celular , Humanos , Interleucina-2/biosíntesis , Hígado/inmunología , Linfoma de Células T/inmunología , Ratones , Datos de Secuencia Molecular , Provirus/inmunología , Ratas , Receptores de Interleucina-2/biosíntesis , Mapeo Restrictivo , Homología de Secuencia de Aminoácido , Transducción de Señal , Bazo/inmunología , Timo/inmunología , Transfección , Células Tumorales CultivadasRESUMEN
To study the possible role of immune selection in the in vivo generation of pathogenic recombinant murine leukemia viruses (MuLV), we have constructed recombinant vaccinia viruses (rVV) expressing the envelope genes of three MuLV: AKR623, MCF247, and MCF13. rVV expressing either AKR623 or MCF247 env could prime H-2b mice for anti-AKR/Gross virus CTL responses, and stimulate the in vitro generation of CTL from the spleens of mice immunized with an AKR/Gross virus-positive lymphoma. MC57 (H-2b) cells infected with either 623EnvVac or 247EnvVac could serve as targets for ARK/Gross virus-specific CTL. Cells infected with the rVV expressing MCF13 env, however, were lysed much less efficiently by these CTL. 13EnvVac was also ineffective in priming or stimulating retrovirus-specific CTL. Finally, experiments with synthetic peptides and minigenes suggested that the reduced immunogenicity of the MCF13 envelope protein likely resulted from a single amino acid substitution within an immunodominant epitope of the p15E (TM) protein. The region of MCF13 env that encodes this epitope is derived from an endogenous xenotropic virus, while the allelic sequences in MCF247 are of ecotropic virus origin. These results suggest the potential for recombination within the MuLV envelope gene to allow escape from host cellular immune responses.
Asunto(s)
Leucemia Experimental/inmunología , Virus Inductores de Focos en Células del Visón/inmunología , Infecciones por Retroviridae/inmunología , Linfocitos T Citotóxicos/inmunología , Infecciones Tumorales por Virus/inmunología , Proteínas del Envoltorio Viral/inmunología , Animales , Secuencia de Bases , ADN Viral , Epítopos/inmunología , Femenino , Antígenos H-2 , Inmunización , Leucemia Experimental/microbiología , Masculino , Ratones , Virus Inductores de Focos en Células del Visón/patogenicidad , Datos de Secuencia Molecular , Infecciones por Retroviridae/microbiología , Infecciones Tumorales por Virus/microbiologíaRESUMEN
H-2b mice are immunologic responders to the tumorigenic MCF1233 murine leukemia virus (MuLV), an AKV-related virus derived from endogenous C57BL MuLV. We have identified an immunodominant CTL epitope that is expressed on MCF1233 MuLV-induced lymphomas of H-2b mice. C57BL/10 (B10) mice were immunized with an MCF1233-induced B10 B cell lymphoma, and tumor-specific CTL cultures were generated in vitro. These were tested for recognition of synthetic class I-binding MuLV peptides, selected for class I allele-specific motifs. One of 28 candidate peptides sensitized target cells for CTL recognition. This peptide seems to be an immuno-dominant epitope, because it was recognized by all independent CTL clones, isolated from the tumor-specific bulk culture. The epitope (KSPWFTTL) is derived from the MCF1233 MuLV envelope (env)-p15E region and is shared by all endogenous AKV types of MuLV. It has an optimal length of eight amino acids and is presented by the Kb H-2 class I molecule. Interestingly, Friend, Moloney, and Rauscher (FMR) types of MuLV are not recognized by MCF MuLV-directed CTL. The FMR env-p15E proteins have a single amino acid difference at the first position of the MCF1233 MuLV epitope (RSPWFTTL instead of KSPWFTTL). The corresponding FMR-encoded peptide bound class I H-2 Kb equally well as the MCF peptide, but it was poorly recognized by MCF1233 MuLV-specific CTL. Moreover, in the Rauscher MuLV-induced cell line RMA the FMr peptide seems not to be processed for recognition by CTL, which was illustrated by experiments with CTL elicited against this peptide. Altered TCR interaction as well as lack of processing thus may explain the type specificity of MCF1233 MuLV-directed CTL.
Asunto(s)
Virus Inductores de Focos en Células del Visón/inmunología , Linfocitos T Citotóxicos/fisiología , Secuencia de Aminoácidos , Animales , Antígenos Virales/química , Antígenos Virales/genética , Línea Celular Transformada , Antígenos H-2/inmunología , Epítopos Inmunodominantes/química , Epítopos Inmunodominantes/genética , Ratones , Ratones Endogámicos C57BL , Virus Inductores de Focos en Células del Visón/genética , Datos de Secuencia Molecular , Homología de Secuencia de Aminoácido , Células Tumorales CultivadasRESUMEN
Infection of certain strains of mice with the ecotropic Friend murine leukemia virus results in the generation of recombinant polytropic mink cell focus-inducing viruses and the development of erythroleukemia. We isolated a Friend mink cell focus-inducing virus (F-MCF-98D) from a Friend murine leukemia virus-infected BALB/c mouse which caused primarily a neurological disease as well as a low incidence of leukemia in susceptible IRW mice. Through genetic studies with the resistant C57BL/10 strain, we identified two genes which correlated with restricted viral replication and resistance to the development of disease caused by F-MCF-98D. One gene correlated with the expression of an endogenous gp70 linked to the Rmcf gene and might act by viral interference. The mechanism of action of the second gene was less clear, but it appeared to be associated with development of an antiviral antibody response.
Asunto(s)
Enfermedades del Sistema Nervioso Central/microbiología , Virus de la Leucemia Murina de Friend/genética , Inmunidad Innata , Virus de la Leucemia Murina/genética , Leucemia Experimental/microbiología , Virus Inductores de Focos en Células del Visón/genética , Animales , Anticuerpos Antivirales/análisis , Formación de Anticuerpos , Células Cultivadas , Enfermedades del Sistema Nervioso Central/inmunología , Cruzamientos Genéticos , Virus de la Leucemia Murina de Friend/inmunología , Virus de la Leucemia Murina de Friend/fisiología , Leucemia Experimental/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos , Virus Inductores de Focos en Células del Visón/inmunología , Virus Inductores de Focos en Células del Visón/fisiología , Especificidad de la Especie , Replicación ViralRESUMEN
The functional and phenotypic characteristics of Ly-4(CD4)+ and Ly-2(CD8)+ T cells were studied after induction of murine AIDS with LP-BM5 murine leukemia virus. Assays of spleen cells for their ability to generate in vitro CTL responses to TNP-modified autologous cells (self + x CTL) and to alloantigens (allo CTL) showed that self + x CTL responses were greatly impaired at 3 to 4 wk postinfection and were undetectable thereafter. Allo CTL responses were normal at 3 to 4 wk, but were reduced at 8 to 9 wk and absent at 14 wk postinfection. This sequential loss of self + x and allo CTL responses was related to a selective defect in Ly-4(CD4)+ Th cell function associated with impaired production of IL-2 and deficient proliferative responses to Con A or to soluble Ag. Changes in the functional characteristics of Ly-4(CD4)+ T cells were unrelated to changes in their frequency in spleen, but did correlate with marked alterations in their distribution among four subsets defined by mAb SM3C11 and SM6C10. Assays of CTL responses generated by mixtures of spleen cells from normal and infected mice suggested that active suppression of Ly-4(CD4)+ Th function may contribute to this defect. Studies of Ly-2(CD8)+ T cells showed that infection with LP-BM5 murine leukemia virus also induced a major phenotypic shift in subpopulations defined by their reactivity with mAb 6C10. However, this phenotypic change did not appear to correlate with major functional defects.
Asunto(s)
Síndromes de Inmunodeficiencia/inmunología , Infecciones por Retroviridae/inmunología , Linfocitos T Citotóxicos/clasificación , Animales , Antígenos Virales/inmunología , Citotoxicidad Inmunológica , Citometría de Flujo , Síndromes de Inmunodeficiencia/microbiología , Terapia de Inmunosupresión , Interleucina-2/biosíntesis , Interleucina-2/inmunología , Isoantígenos/inmunología , Virus de la Leucemia Murina/inmunología , Leucemia Experimental/inmunología , Leucemia Experimental/microbiología , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Virus Inductores de Focos en Células del Visón/inmunología , Fenotipo , Infecciones por Retroviridae/microbiología , Linfocitos T Citotóxicos/inmunologíaRESUMEN
Northern (RNA) analyses were used to study the kinetics of induction of endogenous mink cell focus-forming (MCF) and xenotropic murine leukemia virus (MuLV)-related sequences in NFS and C57BL/6 mice injected with the polyclonal immune activators lipopolysaccharide (LPS), concanavalin A, and 8-bromoguanosine. All three mitogens induced 8.4-, 7.2-, 3.0-, and 1.8-kilobase (kb) MCF-related transcripts coordinately in the spleens of injected mice. Xenotropic MuLV-related expression was also rapidly induced in spleens by the three polyclonal immune activators, but in a noncoordinate manner: a distinct set of transcripts with different kinetics of expression was induced by each mitogen. MCF-related induction after LPS injection was both rapid and sustained; it began within 30 min and persisted for at least 8 days in the spleens of both NFS and C57BL/6 mice. LPS also caused prolonged induction of xenotropic transcripts in spleens of C57BL/6 but not NFS mice. The gld mutation, which causes polyclonal immune activation, induced 8.4-, 10.0-, and 13-kb MCF-related transcripts in C3H/HeJ mice without altering expression of 7.2-, 5.6-, 4.0-, 3.0-, or 1.8-kb MCF-related transcripts. The data demonstrate that individual endogenous MuLV-related transcripts can be induced coordinately or independently and suggest that expression of these transcripts is linked to early stages of lymphocyte activation.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Regulación de la Expresión Génica , Virus de la Leucemia Murina/genética , Virus Inductores de Focos en Células del Visón/genética , ARN Viral/genética , Animales , Concanavalina A/farmacología , Guanosina/análogos & derivados , Guanosina/farmacología , Cinética , Virus de la Leucemia Murina/inmunología , Lipopolisacáridos/farmacología , Hígado/microbiología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Virus Inductores de Focos en Células del Visón/inmunología , Mutación , Hibridación de Ácido Nucleico , Bazo/microbiología , Timo/microbiología , Transcripción GenéticaRESUMEN
We studied the relative importance of class I and class II major histocompatibility complex (MHC) immunoregulation in the control of T- and B-cell lymphomas induced by murine leukemia virus. Previously, we have described a mink cell focus-inducing (MCF) murine leukemia virus, MCF 1233, which induces not only lymphoblastic T-cell lymphomas but also follicle center cell or lymphoblastic B-cell lymphomas. We now report that the outcome of neonatal infection with MCF 1233 in H-2-congenic C57BL/10 and C57BL/6 mice is decisively influenced by the H-2 I-A locus. A total of 64% of H-2 I-Ak, d mice [B10.BR, B10.D2, B10.A(2R), B10.A(4R), and B10.MBR] developed T-cell lymphomas after MCF 1233 infection (mean latency, 37 weeks). In contrast, H-2 I-Ab [B10, B10.A(5R), B6], H-2 I-Ab/k [(B10.A x B10)F1 and (B10 x B10.A)F1], and H-2 I-Abm12 (bm12) mice were resistant against T-cell lymphomagenesis, but 65% of these H-2 I-Ab, b/k, bm12 animals developed B-cell lymphomas (mean latency, 71 weeks). Animals of T-cell lymphoma-susceptible strains that escaped from T-cell lymphomagenesis developed B-cell lymphomas with similar frequency as animals of T-cell lymphoma-resistant strains, but with a shorter latency. H-2 class II-determined regulation of antiviral immunity was reflected in the presence of high titers of antiviral envelope antibodies in T-cell lymphoma-resistant B-cell lymphoma-susceptible H-2 I-Ab, b/k, bm12 mice, whereas in T-cell lymphoma-susceptible H-2 I-Ak,d mice no antiviral antibodies were found. At week 4 after neonatal MCF 1233 infection, a high percentage of thymocytes were virally infected in both T-cell lymphoma-susceptible and -resistant mice. However, T-cell lymphoma-resistant animals cleared the thymic infection between weeks 4 and 10 of age, coinciding with a sharp rise in serum levels of antiviral antibodies. We conclude that the pleiotropic effects of MCF 1233 infection in H-2-congenic mice result from MHC class II I-A-determined T-cell response differences.
Asunto(s)
Genes MHC Clase II , Virus de la Leucemia Murina/inmunología , Linfoma/inmunología , Virus Inductores de Focos en Células del Visón/inmunología , Animales , Anticuerpos Antivirales/biosíntesis , Antígenos Virales/análisis , Linfocitos B , Médula Ósea/microbiología , Susceptibilidad a Enfermedades , Técnica del Anticuerpo Fluorescente , Inmunidad Innata , Leucemia Experimental/inmunología , Linfoma/genética , Linfoma/patología , Ratones , Ratones Mutantes , Virus Inductores de Focos en Células del Visón/fisiología , Bazo/microbiología , Linfocitos T , Timo/microbiologíaRESUMEN
The expression of endogenous retroviral env products on primary leukemia cells of mice was studied with the use of a panel of monoclonal antibodies that discriminate between the various classes of murine leukemia viruses [MuLVs; ecotropic, xenotropic, and mink cell focus-forming (MCF)], as well as between various subtypes within each class. Most spontaneous AKR or Friend MuLV (F-MuLV)- or Moloney MuLV (M-MuLV)-induced AKR or NFS mouse leukemia cells expressed no xenotropic viral envelope antigens but always expressed MCF proteins. Spontaneous C58 lymphomas, on the other hand, often expressed xenotropic proteins in addition to MCF proteins. The subtype of MCF envelope antigens present on leukemia cells, as well as on isolated MCF viruses, varied in a reproducible manner, depending on the mouse strain inoculated and the ecotropic virus used (F-MuLV or M-MuLV). Specifically, F-MuLV consistently induced certain type(s) of MCF envelope antigens on leukemia cells of NFS mice, whereas M-MuLV induced different ones. Similar antigenic patterns were found on the MCF viruses isolated from these mice. Furthermore, MCF envelope antigens (on viruses or leukemia cells) induced in NFS mice by M-MuLV differed from those induced in AKR mice. This finding demonstrated a mouse strain influence on the endogenous MCF env sequences expressed following infection by a given ecotropic virus. The endogenous MCF env sequences in mice thus appear to be a set of genes highly expressed during leukemogenesis, with particular ones specifically expressed in a given mouse strain infected with a given ecotropic virus.
Asunto(s)
Antígenos de Neoplasias/análisis , Antígenos Virales/análisis , Virus de la Leucemia Murina de Friend/inmunología , Virus de la Leucemia Murina/inmunología , Leucemia Experimental/inmunología , Virus Inductores de Focos en Células del Visón/inmunología , Virus de la Leucemia Murina de Moloney/inmunología , Proteínas de Neoplasias/biosíntesis , Proteínas del Envoltorio Viral/biosíntesis , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Antineoplásicos/inmunología , Anticuerpos Antivirales/inmunología , Virus de la Leucemia Murina de Friend/genética , Regulación de la Expresión Génica , Leucemia Experimental/microbiología , Ratones , Ratones Endogámicos/microbiología , Virus Inductores de Focos en Células del Visón/genética , Virus de la Leucemia Murina de Moloney/genética , Proteínas de Neoplasias/inmunología , Proteínas del Envoltorio Viral/inmunologíaRESUMEN
Safety concerns for immunoglobulin preparations have led us to study partition/inactivation of two prototype retroviruses, mouse xenotropic type C and lymphadenopathy-associated virus (LAV) of the acquired immunodeficiency syndrome (AIDS), during manufacture and storage of immunoglobulins. Reduction of infectious retrovirus titers were 10(5) to 10(8)-fold through Cohn-Oncley cold ethanol fractionation from plasma to fraction II, 10(3) to 10(5)-fold through incubation at pH 4.0 and another 10(4)-fold through incubation of the purified liquid immunoglobulin preparations at 27 degrees C or 45 degrees C. The results support the clinical and epidemiological evidence that therapeutic immunoglobulin preparations do not transmit AIDS virus.