scholarly journals Higher Human T-Lymphotropic Virus Type 1 Subtype C Proviral Loads Are Associated With Bronchiectasis in Indigenous Australians: Results of a Case-Control Study

2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Lloyd Einsiedel ◽  
Olivier Cassar ◽  
Emma Goeman ◽  
Tim Spelman ◽  
Virginia Au ◽  
...  

Abstract Background.  We previously suggested that infection with the human T-lymphotropic virus type 1 (HTLV-1) subtype C is associated with bronchiectasis among Indigenous Australians. Bronchiectasis might therefore result from an HTLV-1-mediated inflammatory process that is typically associated with a high HTLV-1 proviral load (PVL). Human T-lymphotropic virus type 1 PVL have not been reported for Indigenous Australians. Methods.  Thirty-six Indigenous adults admitted with bronchiectasis from June 1, 2008, to December 31, 2009 were prospectively recruited and matched by age, sex, and ethno-geographic origin to 36 controls. Case notes and chest high-resolution computed tomographs were reviewed, and pulmonary injury scores were calculated. A PVL assay for the HTLV-1c subtype that infects Indigenous Australians was developed and applied to this study. Clinical, radiological, and virological parameters were compared between groups and according to HTLV-1 serostatus. Results.  Human T-lymphotropic virus type 1 infection was the main predictor of bronchiectasis in a multivariable model (adjusted risk ratio [aRR], 1.84; 95% confidence interval [CI], 1.19–2.84; P = .006). Moreover, the median HTLV-1c PVL (interquartile range) for cases was >100-fold that of controls (cases, 0.319 [0.007, 0.749]; controls, 0.003 [0.000, 0.051] per 100 peripheral blood lymphocytes; P = .007), and HTLV-1c PVL were closely correlated with radiologically determined pulmonary injury scores (Spearman's rho = 0.7457; P = .0000). Other predictors of bronchiectasis were positive Strongyloides serology (aRR, 1.69; 95% CI, 1.13–2.53) and childhood skin infections (aRR, 1.62; 95% CI, 1.07–2.44). Bronchiectasis was the major predictor of death (aRR, 2.71; 95% CI, 1.36–5.39; P = .004). Conclusions.  These data strongly support an etiological association between HTLV-1 infection and bronchiectasis in a socially disadvantaged population at risk of recurrent lower respiratory tract infections.

2007 ◽  
Vol 196 (4) ◽  
pp. 510-521 ◽  
Author(s):  
Olivier Cassar ◽  
Corinne Capuano ◽  
Sylviane Bassot ◽  
Françoise Charavay ◽  
Renan Duprez ◽  
...  

2009 ◽  
Vol 9 (2) ◽  
pp. 159-171 ◽  
Author(s):  
Peter Boross ◽  
Peter Bagossi ◽  
Irene Weber ◽  
Jozsef Tozser

1999 ◽  
Vol 73 (6) ◽  
pp. 4575-4581 ◽  
Author(s):  
Masahiko Makino ◽  
Satoshi Shimokubo ◽  
Shin-Ichi Wakamatsu ◽  
Shuji Izumo ◽  
Masanori Baba

ABSTRACT The development of human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is closely associated with the activation of T cells which are HTLV-1 specific but may cross-react with neural antigens (Ags). Immature dendritic cells (DCs), differentiated from normal donor monocytes by using recombinant granulocyte-macrophage colony-stimulating factor and recombinant interleukin-4, were pulsed with HTLV-1 in vitro. The pulsed DCs contained HTLV-1 proviral DNA and expressed HTLV-1 Gag Ag on their surface 6 days after infection. The DCs matured by lipopolysaccharides stimulated autologous CD4+ T cells and CD8+ T cells in a viral dose-dependent manner. However, the proliferation level of CD4+ T cells was five- to sixfold higher than that of CD8+ T cells. In contrast to virus-infected DCs, DCs pulsed with heat-inactivated virions activated only CD4+ T cells. To clarify the role of DCs in HAM/TSP development, monocytes from patients were cultured for 4 days in the presence of the cytokines. The expression of CD86 Ag on DCs was higher and that of CD1a Ag was more down-regulated than in DCs generated from normal monocytes. DCs from two of five patients expressed HTLV-1 Gag Ag. Furthermore, both CD4+ and CD8+ T cells from the patients were greatly stimulated by contact with autologous DCs pulsed with inactivated viral Ag as well as HTLV-1-infected DCs. These results suggest that DCs are susceptible to HTLV-1 infection and that their cognate interaction with T cells may contribute to the development of HAM/TSP.


Author(s):  
Reza Boostani ◽  
Mina Khodabandeh ◽  
Seyyed Abdolrahim Rezaee ◽  
Houshang Rafatpanah ◽  
Sanaz Ahmadi Ghezeldasht ◽  
...  

2014 ◽  
Vol 289 (32) ◽  
pp. 22284-22305 ◽  
Author(s):  
Elizabeth Jaworski ◽  
Aarthi Narayanan ◽  
Rachel Van Duyne ◽  
Shabana Shabbeer-Meyering ◽  
Sergey Iordanskiy ◽  
...  

2010 ◽  
Vol 84 (10) ◽  
pp. 5124-5130 ◽  
Author(s):  
Rashade A. H. Haynes ◽  
Bevin Zimmerman ◽  
Laurie Millward ◽  
Evan Ware ◽  
Christopher Premanandan ◽  
...  

ABSTRACT Human T-lymphotropic virus type 1 (HTLV-1) infection causes adult T-cell leukemia/lymphoma (ATL) and is associated with a variety of lymphocyte-mediated disorders. HTLV-1 transmission occurs by transmission of infected cells via breast-feeding by infected mothers, sexual intercourse, and contaminated blood products. The route of exposure and early virus replication events are believed to be key determinants of virus-associated spread, antiviral immune responses, and ultimately disease outcomes. The lack of knowledge of early events of HTLV-1 spread following blood-borne transmission of the virus in vivo hinders a more complete understanding of the immunopathogenesis of HTLV-1 infections. Herein, we have used an established animal model of HTLV-1 infection to study early spatial and temporal events of the viral infection. Twelve-week-old rabbits were injected intravenously with cell-associated HTLV-1 (ACH-transformed R49). Blood and tissues were collected at defined intervals throughout the study to test the early spread of the infection. Antibody and hematologic responses were monitored throughout the infection. HTLV-1 intracellular Tax and soluble p19 matrix were tested from ex vivo cultured lymphocytes. Proviral copy numbers were measured by real-time PCR from blood and tissue mononuclear leukocytes. Our data indicate that intravenous infection with cell-associated HTLV-1 targets lymphocytes located in both primary lymphoid and gut-associated lymphoid compartments. A transient lymphocytosis that correlated with peak virus detection parameters was observed by 1 week postinfection before returning to baseline levels. Our data support emerging evidence that HTLV-1 promotes lymphocyte proliferation preceding early viral spread in lymphoid compartments to establish and maintain persistent infection.


1996 ◽  
Vol 1 (4) ◽  
pp. 200-203
Author(s):  
M Nishimura ◽  
S Jacobson ◽  
T Uchiyama ◽  
M Ohta ◽  
T Saida

Human T lymphotropic virus type I (HTLV-I) is a human retrovirus etiologically linked to Adult T cell leukemia (ATL) and HTLV-I associated myelopathyltropical spastic paraparesis (HAM/TSP). Although most HAM/TSP patients have high anti-HTLV-I antibody titers in their sera, HTLV-I infected but seronegative patients with neurological diseases have been reported. To clarify whether seronegative, HTLV-I related neurological disease may exist, we have developed a method that measures the production of interleukin-2 (IL-2) from HTLV-I synthetic peptide-stimulated peripheral blood lymphocytes (PBL) of HTLV-I infected persons. This method is sensitive enough to detect exposure to HTLV-I before seroconversion or even before detection by PCR. We examined 12 patients with chronic progressive myelopathy and eight patients with multiple sclerosis (MS) in central Japan, where the prevalence rate of HTLV-I is between one and four percent among asymptomatic blood donors, using the IL-2 production assay. None of them were positive by the assay, suggesting seronegative HTLV-I myelopathy is very rare among patients with chronic progressive myelopathy and MS in Japan.


Sign in / Sign up

Export Citation Format

Share Document