Neurological aspects of HIV/human T lymphotropic virus coinfection.

Human T lymphotropic virus type 1 is associated with some neurologic diseases, mainly human T lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis. Human T lymphotropic virus type 2 has also been associated with similar cases of human T lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis, but evidences for a definitive relationship are less clear. On the other hand, neurologic manifestations of HIV infection are quite common, affecting more than one third of patients in HIV clinics. Seroepidemiologic studies show that HIV-infected individuals are at an increased risk for human T lymphotropic virus infection and vice versa in comparison with the general population. Furthermore, HIV/human T lymphotropic virus coinfection has been associated with distinctive immunophenotypes and an increased risk for development of neurodegenerative conditions. Thus, studies on HIV/human T lymphotropic virus coinfection have a practice clinical importance. In this review, we aim to discuss clinical and laboratorial data focusing on neurologic diseases in HIV/human T lymphotropic virus coinfection.

Phenotypic and functional changes in gamma delta T lymphocytes from HTLV-1 carriers.

Human T-cell lymphotropic virus type-1 (HTLV-1) is the etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which is a chronic inflammatory disease that leads to gradual loss of motor movement as a result of the death of spinal cord cells through immune mediated mechanisms. The risk to develop HAM/TSP disease positively correlates with the magnitude of HTLV-1 proviral load. Gamma-delta T lymphocytes have been recognized as important players in a variety of infectious diseases. Therefore, we have investigated interactions between HTLV-1 infection and γδ T lymphocytes during HAM/TSP. Similar frequencies of total γδ T lymphocytes and their Vγ9δ2+ and Vγ9δ2neg subpopulations were observed in HAM/TSP patients. However, T lymphocytes obtained from HTLV-1 carriers displayed significantly higher rates of spontaneous proliferation and NKp30 expression when compared to cells from uninfected donors. In addition, an important decrease in the frequency of granzyme B+ γδ T lymphocytes (approximately 50%) was observed in HAM/TSP patients. Higher proportion of IFN-γ+ γδ T lymphocytes was found in HTLV-1-infected patients, which positively correlated with the HTLV-1 proviral load in peripheral blood mononuclear cells. Collectively, our data indicates that HTLV-1 infection leads to phenotypic and functional changes in the population of γδ T lymphocyte population, suggesting that HTLV-1 infection modulates functions associated to these cells, which might be involved in controlling the infection or in the development of HTLV-1-associated diseases.

Protein Profile of Blood Monocytes is Altered in HTLV-1 Infected Patients: Implications for HAM/TSP Disease.

Human T-cell lymphotropic virus type-1 (HTLV-1) is the etiological agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The endothelial breakdown and migration of leukocytes, including monocytes, to the spinal cord are involved in HAM/TSP development. Monocytes from HTLV-1-infected individuals exhibit important functional differences when compared to cells from uninfected donors. Using proteomic shot gun strategy, performed by nanoACQUITY-UPLC system, we analyzed monocytes isolated from peripheral blood of asymptomatic carriers (AC), HAM/TSP and uninfected individuals. 534 proteins were identified among which 376 were quantified by ExpressionE software. Our study revealed a panel of changes in protein expression linked to HTLV-1 infection. Upregulation of heat shock proteins and downregulation of canonical histone expression were observed in monocytes from HTLV-1-infected patients. Moreover, expression of cytoskeleton proteins was increased in monocytes from HTLV-1-infected patients, mainly in those from HAM/TSP, which was confirmed by flow cytometry and fluorescence microscopy. Importantly, functional assays demonstrated that monocytes from HAM/TSP patients present higher ability for adhesion and transmigration thought endothelium than those from AC and uninfected individuals. The major changes on monocyte protein profile were detected in HAM/TSP patients, suggesting that these alterations exert a relevant role in the establishment of HAM/TSP.

Neurological manifestations of coinfection with HIV and human T-lymphotropic virus type 1.

HIV-individuals are at risk for human T-lymphotropic virus (HTLV) coinfection and neurological diseases. Little is known about the impact of HAART among coinfected patients. In this study, 47 out of 428 HIV individuals were coinfected with HTLV (10.9%). Coinfection was an independent variable associated with neurological outcome (odds ratio 8.73). Coinfection was associated with myelopathy [chi square (X(2)) = 93, P < 0.001], peripheral neuropathy (X(2) = 6.5, P = 0.01), and hepatitis C virus infection (X(2) = 36.5, P < 0.001). HAART did not appear to protect against neurological diseases and had no impact on HTLV proviral load.

Adult T-cell leukemia/lymphoma: a case report of primary cutaneous tumoral type.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATLL) is a distinctive peripheral T- lymphocytic malignancy associated with human T-cell lymphotropic virus type 1 (HTLV-1). It may closely resemble other skin lymphomas, particularly mycosis fungoides (MF). CASE REPORT: A 38-year-old woman presented some ellipsoid scaling patches lasting 18 months and developed a large tumoral lesion in the abdomen, which were previously diagnosed as MF. Although histopathologic and immunohistochemistry findings were in consonance with this diagnosis, the fast progression of the disease raised the suspicion that it could represent another type of T-cell lymphoma. The work-up revealed a positive anti-HTLV-1 serology and molecular studies confirmed the monoclonal integration of HTLV-1 provirus into neoplastic cells of the skin, but not into circulating lymphocytes. Extensive investigations were unable to demonstrate any systemic involvement. The final diagnosis was of primary cutaneous type of ATLL. The patient was submitted to a chemotherapy regimen with cyclophosphamide, doxorubicin, vincristine and prednisone, later to conjugated dexamethasone and surgical cytoreduction and then to a second line treatment with gemcitabine, resulting in partial response. A bone marrow heterologous transplantation was performed, but failed to achieve a sustained remission. DISCUSSION: ATLL is a rare lymphoid malignancy in non-endemic HTLV-1 areas, the diagnosis of which could be missed if not highly suspected. In addition to the four subtypes of Shimoyama classification (acute, lymphomatous, chronic and smoldering), a fifth one denominated primary cutaneous and characterized by presence of lesions only in the skin had been proposed and is herein exemplified.