ABSTRACT
BACKGROUND: Japan is endemic for human T-cell leukemia virus type 1 (HTLV-1), and the horizontal transmission of HTLV-1 is often reported. However, the window period (WP) for serologic or molecular screening is unclear. STUDY DESIGN AND METHODS: Results for anti-HTLV-1 screening and confirmatory tests obtained from 648 591 repeated blood donors in the Kyushu district, one of the most endemic areas of HTLV-1 in the world, were evaluated. A lookback study was conducted for seroconverters. RESULTS: During 2012 to 2019, 436 seroconverters (155 men, 281women) were identified with use of a screening chemiluminescence enzyme-immunoassay (CLEIA) and multiple confirmatory tests. Because the period between the latest seronegative donation and seroconversion was highly variable (2.1-276.7 months), 19 cases that seroconverted within 6 months were subjected to the analysis. The WP of the particle agglutination assay and CLEIA was estimated to be 2.2 ± 0.6 and 2.6 ± 1.7 months, respectively. The WP of the indirect immunofluorescence assay was 4.8 ± 6.5 months. Although the WP of western blotting was estimated to be 6.3 ± 8.7 months, four cases were still indeterminate through the study period. Chemiluminescence and line immunoassays, the current screening and confirmatory tests used in the Japanese blood program, showed the shortest WP of 2.2 ± 0.6 months. The WP of real-time polymerase chain reaction for HTLV-1 was estimated to be 4.1 ± 7.8 months. CONCLUSIONS: The WP in commercially available testing systems for HTLV-1/2 was determined for natural infection among repeated blood donors. Considering the HTLV-1 WP will help increase transfusion safety and facilitate the accurate diagnosis of HTLV-1 infection.
Subject(s)
Blood Donors , HTLV-I Antibodies/biosynthesis , HTLV-I Infections/diagnosis , HTLV-II Antibodies/biosynthesis , HTLV-II Infections/diagnosis , Seroconversion/physiology , Viremia/diagnosis , Adult , Aged , Agglutination Tests , DNA, Viral/blood , Early Diagnosis , Endemic Diseases , Female , Follow-Up Studies , HTLV-I Antibodies/blood , HTLV-I Infections/blood , HTLV-I Infections/epidemiology , HTLV-I Infections/prevention & control , HTLV-II Antibodies/blood , HTLV-II Infections/blood , HTLV-II Infections/epidemiology , HTLV-II Infections/prevention & control , Human T-lymphotropic virus 1/immunology , Human T-lymphotropic virus 1/isolation & purification , Human T-lymphotropic virus 2/immunology , Human T-lymphotropic virus 2/isolation & purification , Humans , Immunoenzyme Techniques/methods , Japan/epidemiology , Luminescent Measurements , Male , Mass Screening , Middle Aged , Proviruses/isolation & purification , Real-Time Polymerase Chain Reaction , Retrospective Studies , Time Factors , Viremia/blood , Viremia/epidemiology , Young AdultABSTRACT
In the 239-261 region of the surface glycoprotein of HTLV-I, we delineated five epitopes recognized by antibodies present in sera from HTLV-I infected patients. Three epitopes are located between the amino acids 252 and 261, one is of a linear type and the two others of a conformational type. One epitope is comprised between amino acids 244 and 249. The last epitope described lies between the amino acids 244 and 257 and strictly requires the presence of a serine at position 250 for its recognition. When patients are infected by viral isolates presenting a substitution of the serine at position 250 by a proline, no antibodies recognizing the 244-257 region could be found. Altogether, our data demonstrate that the immunodominant 239-261 region is complex and is subject to antigenic variability.
Subject(s)
Antigenic Variation , HTLV-I Infections/immunology , Human T-lymphotropic virus 1/immunology , Amino Acid Sequence , Epitopes/analysis , Epitopes/chemistry , HTLV-I Antibodies/biosynthesis , Human T-lymphotropic virus 1/genetics , Human T-lymphotropic virus 1/pathogenicity , Humans , Molecular Sequence Data , Peptides/chemical synthesis , Peptides/immunology , Point Mutation , Proline , SerineABSTRACT
Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy (HAM). In asymptomatic carriers and HAM patients, HTLV-1 infection leads to a vigorous cytotoxic T-cell (CTL) response mainly directed to the regulatory Tax protein. In contrast, initial studies showed that anti-HTLV-1 CTL activities were not reproductively detected in ATLL patients, neither ex vivo, nor after in vitro restimulation. To better understand this discrepancy, we explored the anti-HTLV-1 CD8+ T-cell response of eight ATLL patients by using in vitro restimulated or freshly isolated CD8+ T cells. In all the ATLL patients, we found that mitogenic activation allowed the induction of CD8+ T cells able to lyse autologous HTLV-1-infected cells and/or to produce IFNgamma in response to Tax peptides. In contrast, only a minority of the patients possessed CD8+ cells able to respond ex vivo to the same epitopes. These findings indicate that although a restimulatable anti-HTLV-1 CTL activity persists during ATLL, the specific ex vivo response is not constantly maintained. This provides definitive evidence that the CD8+ T-cell response to HTLV-1 is affected by ATLL development and reveals that a major defect concerns the generation and/or the functionality of CD8+ effectors.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Gene Products, tax/immunology , Human T-lymphotropic virus 1/immunology , Leukemia-Lymphoma, Adult T-Cell/immunology , T-Lymphocytes, Cytotoxic/immunology , Cells, Cultured , Chromium/metabolism , HLA-A2 Antigen/analysis , HTLV-I Antibodies/biosynthesis , Humans , Interferon-gamma/metabolism , Leukemia-Lymphoma, Adult T-Cell/classification , Leukemia-Lymphoma, Adult T-Cell/virology , Leukocytes, Mononuclear/immunology , Peptide Fragments/pharmacology , Receptors, Antigen, T-Cell/analysisABSTRACT
Paired samples of cerebrospinal fluid (CSF) and serum from 17 patients with human T-cell lymphotrophic virus I (HTLV-I)-associated myelopathy, 5 patients with multiple sclerosis and 11 controls with non-inflammatory disorders (migraine, idiopathic epilepsy and myelopathy of unknown aetiology) were examined by enzyme-linked immunosorbent assay for the presence of the 60-kDa soluble form of tumour necrosis factor receptor (sTNF-R). The results were compared with blood-CSF barrier function, cell count and the intrathecal synthesis of HTLV-I antibodies. No correlation could be demonstrated. High levels of sTNF-R were found in CSF of patients with HTLV-I-associated myelopathy and multiple sclerosis. In addition, intrathecal sTNF-R was also detected in the patients with non-inflammatory diseases, indicating that sTNF-R is definitively a normal constituent of CSF.
Subject(s)
Blood-Brain Barrier , Central Nervous System Diseases/blood , Central Nervous System Diseases/cerebrospinal fluid , Multiple Sclerosis/blood , Multiple Sclerosis/cerebrospinal fluid , Paraparesis, Tropical Spastic/blood , Paraparesis, Tropical Spastic/cerebrospinal fluid , Receptors, Tumor Necrosis Factor/analysis , Cell Count , HTLV-I Antibodies/biosynthesis , HTLV-I Antibodies/cerebrospinal fluid , Humans , SolubilityABSTRACT
HTLV-I-associated myelopathy, also known as tropical spastic paraparesis (HAM/TSP), is a chronic inflammatory disease of the spinal cord. Acute cases are uncommon. We report the case of a 41-year-old woman with acute HAM/TSP complicated with encephalitis, an intense inflammatory reaction of the nervous system and lymphocytic infiltration of skeletal muscles, liver, salivary, adrenal and pituitary glands. The immunohistochemical studies of the lymphocytes surrounding blood vessels showed both B- and T-lymphocytes, in similar proportion, with both CD4- and CD8-positive cells. In addition, many perivascular and scattered macrophages were observed. Adult T-cell leukemia/lymphoma (ATL) was ruled out. The marrow aspirate was normal. Serial cerebrospinal fluid (CSF) analysis showed presence of HTLV-I antibodies, but without intrathecal synthesis of specific antibodies. Determination of HTLV-I viral loads demonstrated increased levels in the CSF relative to the peripheral blood and may be associated with widespread inflammation. The pathological and immunological findings may help understand the role of immune-reactive cells in the pathogenesis of HTLV-I-associated myelopathy.
Subject(s)
Encephalitis, Viral/virology , Paraparesis, Tropical Spastic/virology , Acute Disease , Adult , Encephalitis, Viral/complications , Encephalitis, Viral/pathology , Encephalomyelitis/complications , Encephalomyelitis/pathology , Encephalomyelitis/virology , Female , HTLV-I Antibodies/biosynthesis , HTLV-I Antibodies/cerebrospinal fluid , HTLV-I Antigens/immunology , Humans , Inflammation/complications , Inflammation/pathology , Inflammation/virology , Paraparesis, Tropical Spastic/cerebrospinal fluid , Paraparesis, Tropical Spastic/complications , Spinal Cord/pathology , Spinal Cord/virologyABSTRACT
Human T-cell leukaemia virus type I (HTLV-I)-transformed rabbit T-cells, F647a, were intraperitoneally injected into eight 10-week-old C3H/He and C3H/HeJ mice (1 x 10(7) F647a cells/mouse), respectively. Antibody titres against HTLV-I increased to a peak at 1-3 months after injection in both C3H/He and C3H/HeJ mice. At 12 months after injection, antibody titres of two of the eight C3H/HeJ mice became undetectable, whereas those of all the C3H/He mice still ranged from 1:10 to 1:40. Sera from both seropositive C3H/He and C3H/HeJ mice reacted with HTLV-I core proteins, but not with the env protein. HTLV-I proviral sequences were detected in two of eight C3H/He mice and three of the eight C3H/HeJ mice. These results suggest that HTLV-I is able to infect an adult mouse.
Subject(s)
HTLV-I Infections/veterinary , Rodent Diseases/transmission , Aging , Animals , Blotting, Western/veterinary , Cell Line , DNA, Viral/analysis , HTLV-I Antibodies/biosynthesis , HTLV-I Infections/transmission , Human T-lymphotropic virus 1/genetics , Human T-lymphotropic virus 1/immunology , Human T-lymphotropic virus 1/isolation & purification , Male , Mice , Mice, Inbred C3H , Polymerase Chain Reaction/veterinary , Proviruses/genetics , Proviruses/isolation & purification , Rabbits , Rodent Diseases/virology , Specific Pathogen-Free OrganismsABSTRACT
To prevent the transmission of human T-lymphotropic virus, type 1 (HTLV-1) during blood transfusion, a program was implemented to screen donors for antibodies to the virus, using a newly developed, passive agglutination (PA) method. During the period April 1986 to March 1987, 675 recipients of donor blood in whom the antibody to HTLV-1 was not present before transfusion were followed for at least 50 days after transfusion. One of these 675 seroconverted despite the transfusion of screened blood, but this seroconversion rate (0.15%) represents a marked decrease from the rate of 8.3 percent prevalent before donor screening began. The rate in the Fukuoka area of donors seropositive for anti-HTLV-1 is 5.34 percent, as detected by the PA method and 1.80 percent, as assessed by the indirect immunofluorescence (IF) technique, with PA-positive but IF-negative blood units thus accounting for 3.5 percent (5.34-1.80) of the total blood donated. The seroconversion rate among recipients transfused with blood screened by IF (at Kyushu University Hospital only) from 1981 to 1985 was 0.41 percent, which was not significantly different from the rate of 0.15 percent observed after PA screening. The discrepancy between PA and IF in the rate of seropositivity was due, in part, to the higher sensitivity of PA in detecting anti-HTLV-1. It is proposed that all donor blood in areas where HTLV-1 is endemic be screened by PA before transfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Blood Donors , HTLV-I Antibodies/analysis , HTLV-I Antigens/immunology , HTLV-I Infections/prevention & control , Transfusion Reaction , Agglutination Tests/methods , Blotting, Western , Fluorescent Antibody Technique , HTLV-I Antibodies/biosynthesis , HTLV-I Infections/transmission , Humans , Prospective Studies , Retrospective StudiesABSTRACT
Mouse monoclonal antibodies to HTLV-1 core proteins, p19 and p24, were obtained by hybridoma technique. The specificity was studied by indirect immunofluorescence, enzyme-linked immunosorbent assay (ELISA), dot blot, and Western blot studies. Polyclonal antibodies reactive with HTLV-1 viral proteins were raised by rabbits and guinea pigs. A sandwich ELISA and a dot blot method using these antibodies detected the soluble viral antigens in the ATL cell lysate and ATL culture media. No reaction was observed when IL-2-activated human T-cell lysate and the culture media were used as controls. These data showed that our sandwich ELISA and dot blot systems are available for quantitative analysis of the soluble HTLV-1 viral antigens and contribute to understanding the ability of viral replication by ATL cells.
Subject(s)
Antibodies, Monoclonal/biosynthesis , HTLV-I Antibodies/biosynthesis , Human T-lymphotropic virus 1/immunology , Animals , Antibodies, Monoclonal/immunology , Antibody Specificity , Enzyme-Linked Immunosorbent Assay , Guinea Pigs , HTLV-I Antibodies/immunology , HTLV-I Antigens/analysis , Immunoblotting , Leukemia-Lymphoma, Adult T-Cell/microbiology , Mice , RabbitsABSTRACT
We intravenously injected Ra-1 cells or MT-2 cells into female adult WKA rats. Spastic paraparesis mainly in the hind-limbs was observed in 1 out of 2 Ra-1 cell-injected WKA rats and in 3 out of 8 MT-2 cell-injected WKA rats 20-27 months after injection. The main neuropathological finding was symmetrical white matter degeneration with mononuclear cell infiltration of the spinal cord, similar to that of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients, and degeneration of nerve roots and peripheral nerves. Antibodies against HTLV-1 antigens were detected in plasma and cerebrospinal fluid from these HAM/TSP-like rats. HTLV-1 provirus was detected from the peripheral blood mononuclear cells of one of these rats 20 months after injection. Interestingly, spastic paraparesis was not observed in F344 rats.
Subject(s)
Disease Models, Animal , Human T-lymphotropic virus 1/pathogenicity , Paraparesis, Tropical Spastic , Animals , Cell Line , Female , HTLV-I Antibodies/biosynthesis , Human T-lymphotropic virus 1/immunology , Humans , Paraparesis, Tropical Spastic/immunology , Rabbits , Rats , Rats, Inbred F344 , Rats, Inbred StrainsABSTRACT
An experimental rabbit model was used to determine host responses to infection by various human T-lymphotropic virus type-I (HTLV-I) strains. Seven groups of 4 to 5 rabbits each were inoculated with lethally-irradiated HTLV-I-infected cell lines derived from patients with adult T-cell leukemia/lymphoma or from patients with HTLV-I-associated myelopathy. Four separate control groups of 2 rabbits each were inoculated with similarly prepared HTLV-I-negative cells derived from rabbits or humans. Anti-viral antibody responses were assessed by immunoblot assay and hematologic parameters were measured using automated cell counters and cytologic staining. The virologic status of challenged rabbits was determined by co-culture and HTLV-I antigen capture assay, as well as by polymerase chain reaction (PCR) amplification of HTLV-I DNA from peripheral blood mononuclear cells (PBMC) or tissues. The HTLV-I inocula could be separated into groups based upon their infectivity to rabbits: highly infectious strains elicited intense serologic responses and were detected frequently in tissues by antigen and PCR assays, while other strains were moderately to poorly infectious, induced weak antibody responses and were infrequently detected by antigen and PCR assays. Overall, PBMC appeared to have the greatest quantity of HTLV-I containing cells, while bone marrow was a poor source of virus. No clinical or hematologic abnormalities were evident during the 24-week course of infection. Taken together, our results suggest there is heterogeneity in the biological response to HTLV-I infection which is, in part, dependent on the infecting strain of virus.
Subject(s)
Deltaretrovirus Infections/physiopathology , Human T-lymphotropic virus 1/pathogenicity , Leukemia, T-Cell/microbiology , Paraparesis, Tropical Spastic/microbiology , Animals , Blotting, Western , DNA, Viral/analysis , Genes, gag , HTLV-I Antibodies/biosynthesis , HTLV-I Antigens/immunology , Humans , Polymerase Chain Reaction , RabbitsABSTRACT
Pig-tailed macaques were vaccinated with a human T-cell lymphotropic virus type I (HTLV-I) subunit vaccine. Vaccinates and controls were challenged with simian T-cell lymphotropic virus type I (STLV-I)-infected cells. Vaccination yielded antibody responses to HTLV-I and STLV-I gag and env precursors. Controls developed HTLV-I and STLV-I antibody to gag and tax protein. Immunization produced syncytium inhibiting antibody and cellular cytotoxicity to virus-infected cells. Reverse transcriptase activity was present in control macaques only, implying that the subunit vaccine was protective against STLV-I infection.
Subject(s)
Human T-lymphotropic virus 1/immunology , Retroviridae Infections/prevention & control , Simian T-lymphotropic virus 1/immunology , Viral Vaccines/immunology , Animals , Antibodies, Viral/biosynthesis , Antibody-Dependent Cell Cytotoxicity , Antigens, Viral/immunology , Blotting, Western , Cell Line , Gene Products, env/immunology , Gene Products, gag/immunology , Giant Cells , HTLV-I Antibodies/biosynthesis , Macaca nemestrina , VaccinationABSTRACT
Synthetic peptides derived from the env protein of human T-lymphotropic virus type I (HTLV-I) were used to identify the immunodominant motifs in rhesus macaques naturally infected with simian T-lymphotropic virus type I (STLV-I). Of the 13 peptides derived from the env protein of HTLV-I, Env-1(191-214) and Env-5(242-257) reacted with 81% (44/54) and 54% (29/54) of specimens from infected monkeys, respectively. A recombinant protein (MTA-I162-209) reacted with 53 of 54 (98%) STLV-I-infected serum specimens. While similar immune reactivities to Env-1 and MTA-1 were observed in both HTLV-I-infected human sera and STLV-I-infected monkey sera, the reactivity to Env-5 was significantly higher in HTLV-I-infected human sera. Differential reactivities may be attributed to the differences in the secondary structures of the STLV-I and HTLV-I envelope protein in the Env-5 region, since homologous peptide with STLV-I sequence did not result in enhanced sensitivity of anti-Env-5 antibody detection.
Subject(s)
Gene Products, env/immunology , HTLV-I Antibodies/biosynthesis , HTLV-I Antigens/immunology , Immunodominant Epitopes/immunology , Retroviridae Infections/immunology , Simian T-lymphotropic virus 1/immunology , Amino Acid Sequence , Animals , Gene Products, env/chemistry , Macaca mulatta , Molecular Sequence Data , Peptide Fragments/chemical synthesis , Peptide Fragments/immunology , Retroviridae Infections/microbiology , Retroviridae Proteins, Oncogenic/chemistry , Retroviridae Proteins, Oncogenic/immunology , env Gene Products, Human Immunodeficiency VirusABSTRACT
The presence or absence of the anti-human T-cell leukemia virus type (HTLV-I) antibody and the HTLV-I proviral genome was examined in the offspring of inbred rabbits, which were born to HTLV-I carrier does. The results showed that not all offspring born to the carriers were infected and that not all the infected offspring seroconverted at the age of 10 weeks, which is similar to observations made in human carriers. The anti-HTLV-I antibody was assayed by indirect immunofluorescence in 55 offspring at the age of 10 weeks, which were born to B/J or (B/J x Chbb:HM)F1 seropositive HTLV-I carrier does. Twelve out of 31 offspring born from F1 x F1 mating were seropositive, whereas none of 24 offspring born from B/J x B/J mating, F1 x B/J mating, or F1 x Chbb:HM mating were seropositive. The polymerase chain reaction (PCR) method revealed the presence of the HTLV-I proviral genome in 18 out of 23 offspring born from F1 x F1 mating (F2 hybrids). In these 18 HTLV-I-infected F2 hybrids, 8 were seropositive and 10 were seronegative. The major histocompatibility complex (MHC) of these 23 F2 hybrids was analyzed by restriction fragment length polymorphism (RFLP) in southern hybridization. The results showed no close correlation of MHC with HTLV-I susceptibility or with seroconversion. Natural infection via mother-to-child transmission of virus seems to produce seronegative as well as seropositive carriers. This rabbit model may be useful for the study of seronegative virus carriers via mother-to-child transmission of HTLV-I.
Subject(s)
HTLV-I Antibodies/biosynthesis , HTLV-I Infections/transmission , Maternal-Fetal Exchange , Animals , Animals, Newborn , Base Sequence , Carrier State , Crosses, Genetic , Female , HTLV-I Infections/genetics , HTLV-I Infections/immunology , Major Histocompatibility Complex/genetics , Molecular Sequence Data , Polymorphism, Restriction Fragment Length , Pregnancy , Proviruses/immunology , RabbitsABSTRACT
Recombinant vaccinia viruses (RVV) designated RVV E1, RVV E2, and RVV E3, were constructed to express three different versions of the human T cell leukemia virus type I (HTLV-I) envelope proteins to determine which configuration elicits an optimal antibody response. RVV E1 expressed the native HTLV-I envelope proteins gp46 (surface protein) and gp21 (transmembrane protein), while RVV E2 expressed the envelope precursor with the proteolytic cleavage site deleted. The RVV E3 construct expressed only the external surface glycoprotein, gp46. Radioimmunoprecipitation and FACS analysis confirmed that the appropriate envelope proteins were expressed by RVV E1-, E2-, and E3-infected cells. Immunization studies were carried out using Balb/c, A/J, and C57BL/6 strains of mice. Balb/c mice responded poorly to immunization with all of the three RVV constructs. C57BL/6 mice produced neutralizing antibodies in response to immunization with all three constructs, whereas A/J mice developed neutralizing antibodies only when immunized with the RVV E1s construct. The results indicate that the humoral immune responses depend on the form of HTLV-I envelope proteins expressed by each RVV.
Subject(s)
Gene Products, env/immunology , HTLV-I Antibodies/immunology , Retroviridae Proteins, Oncogenic/immunology , Animals , Fluorescent Antibody Technique , HTLV-I Antibodies/biosynthesis , L Cells , Mice , Mice, Inbred C57BL , Neutralization Tests , Precipitin Tests , Radioimmunoprecipitation Assay , Recombinant Proteins/immunology , Vaccinia virus/genetics , env Gene Products, Human Immunodeficiency VirusABSTRACT
Two groups of 3 rabbits each were immunized with either recombinant vaccinia virus, WR-SFB5env, carrying the human T-cell lymphotropic virus type I (HTLV-I) env gene at the site of the hemagglutinin gene of the WR strain, or control vaccinia virus, HA-WR, lacking the functional hemagglutinin gene. All 6 rabbits responded with anti-vaccinia virus antibodies. WR-SFB5env elicited anti-HTLV-I env antibodies but no vesicular stomatitis virus (HTLV-I) pseudotype neutralizing antibodies in all 3 rabbits. After 10 weeks, the animals were challenged by transfusion of blood from an HTLV-I-infected rabbit. Two of the 3 vaccinated rabbits and all 3 control rabbits became infected with HTLV-I, as indicated by seroconversion and detection of HTLV-I proviral sequences by polymerase chain reaction. The rabbit that had been protected from initial challenge became infected with HTLV-I upon rechallenge 12 weeks after the first challenge. In view of the proven prophylactic effect of passive immunization against HTLV-I, our vaccine trial failed because WR-SFB5env was incapable of inducing neutralizing antibodies against HTLV-I in the immunized animals. It remains to be studied whether cell-mediated immunity such as antibody-dependent cellular cytotoxicity was involved in the temporary protection of I vaccinated rabbit.
Subject(s)
HTLV-I Antibodies/biosynthesis , HTLV-I Infections/prevention & control , Human T-lymphotropic virus 1/genetics , Vaccines, Synthetic , Viral Vaccines , Animals , Blotting, Western , Drug Evaluation, Preclinical , Genes, env/immunology , HTLV-I Antibodies/blood , Human T-lymphotropic virus 1/immunology , Neutralization Tests , Polymerase Chain Reaction , Rabbits , Vaccinia virus/immunology , Vesicular stomatitis Indiana virus/immunologyABSTRACT
Prophylactic effect of human T cell leukemia virus type I (HTLV-I) immune globulin (HTLVIG) against milkborne transmission of HTLV-I was investigated in a rabbit model. Four litters (A-D: 7, 5, 7, and 7 offspring, respectively) born to an HTLV-I-infected rabbit were used. Litters A and D were allowed to grow normally as controls, while litters B and C were given weekly intraperitoneal inoculation of HTLVIG four times until weaning at 4.5 weeks of age. Only 1 (8.3%) of the 12 HTLVIG-inoculated rabbits, compared with 6 (42.9%) of the 14 control rabbits, seroconverted for HTLV-I. Gene amplification detected the presence of HTLV-I proviral sequences in all of the seroconverted but in none of the seronegative rabbits. These results suggest that passive immunization is effective in preventing dam-to-offspring transmission of HTLV-I.
Subject(s)
HTLV-I Antibodies/therapeutic use , HTLV-I Infections/prevention & control , Immunization, Passive , Immunoglobulins, Intravenous/therapeutic use , Milk/microbiology , Animals , Blotting, Western , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Female , HTLV-I Antibodies/biosynthesis , HTLV-I Infections/transmission , Immunoglobulin G/biosynthesis , Immunoglobulin G/therapeutic use , Immunoglobulin M/biosynthesis , Polymerase Chain Reaction , Pregnancy , RabbitsABSTRACT
The susceptibilities of different strains of inbred rats to infection with the human T-cell leukemia virus (HTLV-I) after inoculation of human HTLV-I producer cell lines were compared. The Fisher F344 and Brown Norway strains developed the highest antibody response to HTLV-I, while the Lewis and BB strains were low responders. Antibodies against the HTLV-I gag proteins, and env gp21 but not env gp46, were detected in Western blots with sera from HTLV-I-infected Fischer F344 and Brown Norway rats. These sera were inactive in an in vitro syncytium-formation inhibition test. The HTLV-I provirus was detected by polymerase chain reaction in all Fischer F344, and some Lewis and Brown Norway rats, but not in the BB, which lack CD8+ T lymphocytes. The most frequent locations of the HTLV-I provirus in the Fischer F344, Lewis and Brown Norway rats at 12 weeks after infection were the peripheral blood mononuclear cells (PBMC) and spinal cord. In a second experiment in Brown Norway rats, the provirus was again detected in the PBMC of rats at 12 weeks, but not at 22 weeks, and among the other organs tested at 22 weeks the sympathetic nerve ganglia were positive. It is concluded that HTLV-I infection occurs in adult rats, but is suppressed with time.
Subject(s)
HTLV-I Antibodies/biosynthesis , HTLV-I Infections/immunology , Human T-lymphotropic virus 1/pathogenicity , Proviruses , Rats, Inbred Strains/immunology , Rats, Inbred Strains/microbiology , Animals , Blotting, Western , Central Nervous System/microbiology , Genome, Viral , HTLV-I Antigens/immunology , Human T-lymphotropic virus 1/immunology , Humans , Immunity, Cellular , Lymph Nodes/microbiology , Polymerase Chain Reaction , Proviruses/genetics , Rats , Rats, Inbred Strains/physiologyABSTRACT
We have compared the immunoglobulin isotype and IgG subclass and the titre of neutralizing antibody responses to the human T cell lymphotropic virus type I (HTLV-I) between a group of asymptomatic HTLV-I infected individuals and a group with the neurological disease HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). A western blot titration assay and an envelope peptide ELISA were used to determine the presence and titre of isotype and IgG subclass responses to the gag p19 and p24 proteins and to the envelope protein. Significant increases were observed in the number of individuals seropositive for a particular isotype and IgG subclass in the HAM/TSP group versus the asymptomatic group particularly for IgM and IgE and to a lesser extent, IgA. The predominant IgG subclasses to the HTLV-I p19, p24 and envelope proteins were IgG1 and IgG3. This finding was also observed in the titres of the antibody responses to these HTLV-I proteins. The HAM/TSP group also exhibited significantly higher neutralizing antibody titres than the asymptomatic group. This evidence suggests that some form of chronic immune stimulation might be involved in the immunopathogenesis of HAM/TSP. In addition, by following the Western blot titre to the IgM and IgE isotypes in particular, it may be possible to identify asymptomatic individuals progressing to HAM/TSP.
Subject(s)
Gene Products, env/immunology , Gene Products, gag/immunology , HTLV-I Antibodies/biosynthesis , HTLV-I Infections/immunology , Human T-lymphotropic virus 1/immunology , Paraparesis, Tropical Spastic/immunology , Enzyme-Linked Immunosorbent Assay , HTLV-I Antibodies/classification , Humans , Immunoglobulin G/biosynthesis , Immunoglobulin G/classification , Immunoglobulin Isotypes/biosynthesis , Retroviridae Proteins, Oncogenic/immunology , env Gene Products, Human Immunodeficiency Virus , gag Gene Products, Human Immunodeficiency VirusABSTRACT
Rabbits experimentally infected with HTLV-I and HIV-1 produced antibody to various viral proteins, and viral DNA could be detected by gene amplification using the polymerase chain reaction. HTLV-I genes were detected in cell lines derived from infected rabbits, and in some cases, both HIV-1 and HTLV-I DNA sequences were demonstrated in peripheral blood cells taken from rabbits one year after experimental infection. The polymerase chain reaction procedure was used to demonstrate the presence of HTLV-I gag, env and tax genes and HIV-1 gag and env genes. The amplified fragments were identified by size and by hybridization to specific probes. The ability of rabbits to support simultaneous infection with HTLV-I and HIV-1 will allow in vivo studies of the possible synergistic effects of these important human pathogens.
Subject(s)
Acquired Immunodeficiency Syndrome/complications , HIV-1 , HTLV-I Infections/complications , Acquired Immunodeficiency Syndrome/immunology , Acquired Immunodeficiency Syndrome/microbiology , Animals , Cell Line, Transformed , DNA, Viral/genetics , DNA, Viral/isolation & purification , Disease Models, Animal , Gene Amplification , Genes, Viral , HIV Antibodies/biosynthesis , HIV-1/genetics , HTLV-I Antibodies/biosynthesis , HTLV-I Infections/immunology , HTLV-I Infections/microbiology , Human T-lymphotropic virus 1/genetics , RabbitsABSTRACT
A synthetic peptide derived from the external glycoprotein of human T cell lymphotropic virus type I (HTLV-I) (Env-5; amino acids 242 to 256) reacted with IgG antibodies in serum specimens from HTLV-I-infected individuals. C-terminal residues of Env-5 were crucial for the antibody reactivity. Polyclonal rabbit antibodies to Env-5 did not inhibit syncytium formation but such antibodies reacted specifically with gp68env and gp46env glycoproteins of HTLV-I in an immunoblot analysis. Immunoprecipitation of the surface-labelled MT-2 (HTLV-I-infected) cell line with anti-Env-5 precipitated the gp68env precursor protein. It was concluded that peptide Env-5 mimics a surface-exposed epitope on the HTLV-I external glycoprotein.