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https://www.arca.fiocruz.br/handle/icict/49072
PATHOGENESIS OF HTLV-1 INFECTION AND PROGRESSION BIOMARKERS: AN OVERVIEW
Author
Affilliation
Federal University of Bahia. Professor Edgard Santos University Hospital Complex. Laboratory of Infectious Diseases Research, Salvador, BA, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, Brasil.
Federal University of Pará. Nucleus of Tropical Medicine. Belém, PA, Brazil.
Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil.
Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil.
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Laboratório Avançado de Saúde Pública. Salvador, BA, Brasil.
Federal University of Pará. Nucleus of Tropical Medicine. Belém, PA, Brazil.
Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil.
Federal University of Pará. Institute of Biological Sciences. Laboratory of Virology. Belém, PA, Brazil.
Abstract
Infection by human T-cell lymphotropic virus type 1 (HTLV-1) occurs in lymphocytes,
which travel throughout the body, thus affecting several target organs and causing varied
clinical outcomes, particularly in populations that are underserved and do not have access
to healthcare. However, the mechanism of pathogenesis is not yet fully understood. The
TAX and HTLV-1 basic leucine zipper factor (HBZ) proteins maintain viral persistence and
affect pathogenesis through cell proliferation and immune and inflammatory responses
that accompany each clinical manifestation. TAX expression leads to inhibition of transcription
error control, OX40 overexpression, and cell proliferation in adult T-cell leukemia
(ATL). OX40 levels are elevated in the central nervous system (CNS), and the expression of
TAX in the CNS causes neuronal damage and loss of immune reactivity among patients
with HTLV-1-associated myelopathy (HAM). HBZ reduces viral replication and suppresses
the immune response. Its cell compartmentalization has been associated with the pathogenesis
of HAM (cytoplasmic localization) and ATL (nuclear localization). TAX and HBZ
seem to act antagonistically in immune responses, affecting the pathogenesis of HTLV-1
infection. The progression from HTLV-1 infection to disease is a consequence of HTLV-1
replication in CD4+ T and CD8+ T lymphocytes and the imbalance between proinflammatory
and anti-inflammatory cytokines. The compartmentalization of HBZ suggests that this
protein may be an additional tool for assessing immune and inflammatory responses, in
addition to those already recognized as potential biomarkers associated with progression
from infection to disease (including human leukocyte antigen (HLA), killer immunoglobulin-
like receptors (KIR), interleukin (IL)-6, IL-10, IL-28, Fas, Fas ligand, interferon (IFN)-g,
tumor necrosis factor (TNF)-a, and mannose-binding lectin).
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