HTLV: virus linfotrópico de células T humanas. Historia de un virus milenario y la importancia en el descubrimiento de las migraciones humanas / HTLV: lymphotropic virus of human t-cells. The history of an ancient virus and its significance of human migrations

El virus HTLV I/II es un retrovirus, muy antiguo, cuyo origen posiblemente sea su homólogo en los simios, quienes lo transmiten al humano y luego se difunde entre nuestra especie. Gracias a los adelantos científicos, se han podido establecer las tres probables entradas o rutas migratorias de nuestros antepasados entre los distintos continentes. Ellos lamentablemente desconocían que estaban infectados. En nuestros tiempos, este insignificante y tan pequeño virus presenta áreas endémicas en todo el mundo (inclusive Argentina) y es el responsable de dos enfermedades, la Paraparesia Espástica Tropical y la Leucemia T del adulto, ambas incurables. Se ha podido prevenir la diseminación del mismo por el desarrollo de pruebas de tamizaje o selección (enzimoinmunoensayo) y suplementarias (Western Blot), como también por el asesoramiento médico de los individuos infectados. (AU)

HTLV: virus linfotrópico de células T humanas. Historia de un virus milenario y la importancia en el descubrimiento de las migraciones humanas / HTLV: lymphotropic virus of human t-cells. The history of an ancient virus and its significance of human migrations

El virus HTLV I/II es un retrovirus, muy antiguo, cuyo origen posiblemente sea su homólogo en los simios, quienes lo transmiten al humano y luego se difunde entre nuestra especie. Gracias a los adelantos científicos, se han podido establecer las tres probables entradas o rutas migratorias de nuestros antepasados entre los distintos continentes. Ellos lamentablemente desconocían que estaban infectados. En nuestros tiempos, este insignificante y tan pequeño virus presenta áreas endémicas en todo el mundo (inclusive Argentina) y es el responsable de dos enfermedades, la Paraparesia Espástica Tropical y la Leucemia T del adulto, ambas incurables. Se ha podido prevenir la diseminación del mismo por el desarrollo de pruebas de tamizaje o selección (enzimoinmunoensayo) y suplementarias (Western Blot), como también por el asesoramiento médico de los individuos infectados.

Electron microscopic observation of a Brazilian HTLV-I isolated.

Several studies carried out in Brazil have shown a high incidence of HTLV-I infection among the general population and in different groups, such as blood donors, hemophiliacs, hematological and neurological patients. Cases of adult T-cell leukemia/lymphoma as well as tropical spastic paraparesis/HTLV-I associated myelopathy have already been described. Therefore, it is important to characterize Brazilian HTLV strains using different technical approaches. The purpose of this paper is to characterize and recognize HTLV particles employing routine and immunoelectron microscopy in lymphocyte cocultures. Ultrastructural analysis showed typical large and small virus particles in close relation with the lymphocyte membrane. Immunoelectron microscopy, carried out with HTLV positive sera, allowed the identification of the virus as a type C oncovirus, group HTLV-BLV. The first interaction events between virus and lymphocyte membrane have also been analysed and structures related to the endocytic route for HTLV entrance were pointed out.

Ultrastructural aspects of the human T-lymphotropic virus type I (HTLV-I) in Brazil

Nowadays, Brazil may be considered an endemic area for HTLV-I infection. Several studies showed a high incidence of HTLV-I infection among the general population and different groups such as blood donors, hemophiliacs, hematological and neurological patients. Cases of adult T-cell leukemia/lymphoma as well as tropical spastic paraparesis/HTLV-I associated myelopathy have been already described. Therefore the use of different technical approaches, to characterize Brazilian HTLV strains has become important. HTLV particles were characterized and recognized by the use of transmission electron microscopy in lymphocyte cocultures. The ultra-structural analysis revealed typical virus particles close to the lymphocyte membrane. The immunoelectron microscopy allowed the identification of the virus as HTLV, a type C oncovirus, group HTLV-BLV. The ethanol phosphotungstic acid technique showed structures similar to the virus budding process and the routine preparations have contributed to the analysis of the first virus-cell interaction events. Structures related to the endocytic route HTLV entrance are also pointed out.

Detection and isolation of human T-cell leukemia/lymphoma virus type I (HTLV-I) from cultured lymphocytes of a Brazilian TSP/HAM patient.

Some Brazilian regions are considered to be endemic for human T-cell leukemia/lymphoma virus type I (HTLV-I) infection. Several studies have shown a high prevalence of HTLV-I infection among different groups such as blood donors, hemophiliacs and patients suffering from hematological and neurological diseases. Cases of adult T-cell leukemia/lymphoma as well as tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) have already been described in Brazil. We report the isolation of an HTLV-I strain from cultured lymphocytes of a TSP/HAM patient. An IL-2-dependent HTLV-I-infected T-cell line (ROB) expressing viral antigens was established and reverse transcriptase activity could be detected in the culture supernatant. Ultrastructural analysis showed immature and mature HTLV retrovirus particles. Finally, HTLV-I provirus type I was demonstrated by the polymerase chain reaction. This is the first isolation completely carried out in Latin America. The molecular analysis of viral strains, now in progress, should clarify the molecular epidemiology of HTLV-I in Brazil.

Detection and isolation of human T-cell leukemia/lymphoma virus type I (HTLV-I) from cultured lymphocytes of a Brazilian TSP/HAM patient

Some Brazilian regions are considered to be endemic for human T-cell leukemia/lymphoma virus type I (HTLV-I) infection. Several studies have shown a high prevalence of HTLV-I infection among different groups such as blood donors, hemophiliacs and patients suffering from hematological and neurological diseases. Cases of adult T -cell leukemia/lymphoma as well as tropical spastic paraparesis/HTLV-i-infected T -cell line (ROB) expressing viral antigens was established and reverse transcriptase activity could be detected in the culture supernatant. Ultrastructural analysis showed immature and mature HTLV retrovirus particles. Finally, HTLV-I provirus type I was demonstrated by the plymerase chain reaction. This is the first isolation completely carried out in Latin America. The molecular analysis of viral strains, now in progress, should clarify the molecular epidemiology of HTLV-I in Brazil

Cell surface phenotype and human T lymphotropic virus type 1 antigen expression in 12 T cell lines derived from peripheral blood and cerebrospinal fluid of West Indian, Guyanese and African patients with tropical spastic paraparesis.

Twelve long-term cell lines were established from peripheral blood mononuclear cells (PBMC) or cerebrospinal fluid cells of patients with human T lymphotropic virus type I (HTLV-1) seropositive tropical spastic paraparesis (TSP) originating from the French West Indies, French Guyana or the Central African Republic. Most of these long-term interleukin-2-dependent cell lines exhibited a pattern characteristic of CD4(+)-activated T cells with high expression of CD2, CD3 and CD4 antigens, associated with a strong density of TAC and DR molecules. Nevertheless, in five cases CD8 expression was present at a significant level. HTLV-I antigens were never detected in uncultured PBMC, but they were expressed in a few cells after short-term culture and after 4 months the majority of the cells were HTLV-I positive, as demonstrated by indirect immunofluorescence (IF) using polyclonal or monoclonal anti-p19 and anti-p24 antibodies. Low and variable levels of reverse transcriptase activity were detected in supernatant fluids of these cell lines only after 4 months of culture, when at least 50% of the cells exhibited HTLV-I antigens by IF. However, numerous type C HTLV-I-like viral particles were detected, mostly in the extracellular spaces, with rare budding particles. Similar findings were found in three T cell lines derived from West Indian and African patients with adult T-cell leukaemia/lymphoma (ATLL). Differences in high Mr polypeptides were detected by Western blot in cell lysates when comparing TSP- or ATLL-derived T cell lines. Thus a signal of 62K was easily detectable in all the TSP lines, but not in the ATLL lines. In all cell lines bands corresponding to p53, p24 and p19 viral core polypeptides were present, as was the env gene-coded protein p46.

Cell surface phenotype and human T lymphotropic virus type 1 antigen expression in 12 T cell lines derived from peripheral blood and cerebrospinal fluid of West Indian, Guyanese and African patients with tropical spastic paraparesis

Twelve long term cell lines were established from peripheral blood mononuclear cells (PBMC) or cerebrospinal fluid cells of patients with human T lymphotropic virus type I (HTLV-I) seropositive tropical spastic paraparesis (TSP) originating from the French West Indies, French Guyana or the Central African Republic. Most of these long term interlukin-2-dependent cell lines exhibited a pattern characteristic of CD4+ -activated T cells with high expression of CD2, CD3 and CD4 antigens, associated with a strong density of TAC and DR molecules. Nevertheless, in five cases CD8 expression was present at a significant level. HTLV-I antigens were expressed in a few cells after short-term culture and after 4 months the majority of the cells were HTLV-I positive, as demonstrated by indirect immunofluorescence (IF) using polyclonal or monoclonal anti-p19 and anti-p24 antibodies. Low and variable levels of reverse transcriptase activity were detected in supernatant fluids of these cell lines only after 4 months of culture, when at least 50 percent of the cells exhibited HTLV-I antigens by IF. However numerous type C HTLV-I-like viral particles were detected, mostly in the extracellular spaces, with rare budding particles. Similar findings were found in three T cell lines derived from West Indian and African patients with adult T-cell leukaemia/lymphoma (ATLL). Differences in high M-r polypeptides were detected by Western blot in cell lysates when comparing TSP-or ATLL-derived T cell lines. Thus a signal of 62K was easily detectable in all the TSP lines, but not in the ATLL lines. In all cell lines bands corresponding to p53, p24 and p19 viral core polypeptides were present, as was the env gene-coded protein p46. (AU)