HTLV-I proviral DNA amount correlates with infiltrating CD4+ lymphocytes in the spinal cord from patients with HTLV-I-associated myelopathy

Kubota, Ryuji; Umehara, Fujio; Izumo, Shuji; Ijichi, Shinji; Matsumuro, Kenji; Yashiki, Shinji; Fujiyoshi, Toshinobu; Sonoda, Shunro; Osame, Mitsuhiro

doi:10.1016/0165-5728(94)90060-4

Cited by 95 publications

(56 citation statements)

References 29 publications

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“…T cells, compared to patients with a shorter duration of disease (Umehara et al, 1993;Kubota et al, 1994;Lehky et al, 1995;Moritoyo et al, 1996). Collectively, these studies suggest that the ability to detect proviral DNA and viral gene expression within the CNS may vary with the duration of disease.…”

Section: Overview Of the Pathogenic Processmentioning

confidence: 90%

See 1 more Smart Citation

Human T cell leukemia virus type I and neurologic disease: Events in bone marrow, peripheral blood, and central nervous system during normal immune surveillance and neuroinflammation

Grant

Barmak

Alefantis

et al. 2002

Journal Cellular Physiology

101

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Human T cell lymphotropic/leukemia virus type I (HTLV‐I) has been identified as the causative agent of both adult T cell leukemia (ATL) and HTLV‐I‐associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the exact sequence of events that occur during the early stages of infection are not known in detail, the initial route of infection may predetermine, along with host, environmental, and viral factors, the subset of target cells and/or the primary immune response encountered by HTLV‐I, and whether an HTLV‐I‐infected individual will remain asymptomatic, develop ATL, or progress to the neuroinflammatory disease, HAM/TSP. Although a large number of studies have indicated that CD4+ T cells represent an important target for HTLV‐I infection in the peripheral blood (PB), additional evidence has accumulated over the past several years demonstrating that HTLV‐I can infect several additional cellular compartments in vivo, including CD8+ T lymphocytes, PB monocytes, dendritic cells, B lymphocytes, and resident central nervous system (CNS) astrocytes. More importantly, extensive latent viral infection of the bone marrow, including cells likely to be hematopoietic progenitor cells, has been observed in individuals with HAM/TSP as well as some asymptomatic carriers, but to a much lesser extent in individuals with ATL. Furthermore, HTLV‐I+ CD34+ hematopoietic progenitor cells can maintain the intact proviral genome and initiate viral gene expression during the differentiation process. Introduction of HTLV‐I‐infected bone marrow progenitor cells into the PB, followed by genomic activation and low level viral gene expression may lead to an increase in proviral DNA load in the PB, resulting in a progressive state of immune dysregulation including the generation of a detrimental cytotoxic Tax‐specific CD8+ T cell population, anti‐HTLV‐I antibodies, and neurotoxic cytokines involved in disruption of myelin‐producing cells and neuronal degradation characteristic of HAM/TSP. J. Cell. Physiol. 190: 133–159, 2002. © 2002 Wiley‐Liss, Inc.

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Section: Overview Of the Pathogenic Processmentioning

confidence: 90%

“…T cells, CD8 T cells, and activated macrophages and microglial cells in and around the sites of CNS lesions¯uctuate with duration of disease (Umehara et al, 1993;Kubota et al, 1994;Moritoyo et al, 1996). Therefore, the numbers of HTLV-I cells in the CNS would also be expected to change during this transition.…”

Section: Overview Of the Pathogenic Processmentioning

confidence: 99%

Human T cell leukemia virus type I and neurologic disease: Events in bone marrow, peripheral blood, and central nervous system during normal immune surveillance and neuroinflammation

Grant

Barmak

Alefantis

et al. 2002

Journal Cellular Physiology

101

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“…[38][39][40][41][42][43] Consequently, substantial proportions of the CD4 T cells in the periphery may be infected. Proviral loads during the long asymptomatic phase of infection are lower than in TSP/HAM, although they may be as high as 1/25 PBMCs.…”

Section: High Circulating Proviral Loads Characterize Htlv-1 Infectionmentioning

confidence: 99%

“…Proviral loads during the long asymptomatic phase of infection are lower than in TSP/HAM, although they may be as high as 1/25 PBMCs. [38][39][40][41][42][43] Here, there is evidence of an extensive replication, yet HTLV-1 is genetically more stable than any other RNA virus. HIV proviral loads in late-stage disease, AIDS, may reach up to 1/100 to 1/30 in the periphery.…”

Section: High Circulating Proviral Loads Characterize Htlv-1 Infectionmentioning

confidence: 99%

Molecular and cellular aspects of HTLV-1 associated leukemogenesis in vivo

2003

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“…Fax j33 1 40 61 31 67. e-mail sozd!pasteur.fr observed by PCR in the CNS of TSP\HAM patients (Bhigjee et al, 1991 ;Kira et al, 1992 ;Kubota et al, 1994). However, from these experiments it is impossible to know whether the provirus DNA was present in peripheral blood lymphocytes or in neural cells.…”

mentioning

confidence: 99%