Recombinant Human T-Cell Lymphotropic Virus Type I gp21+gp46 chimeric antigen

Background Human immunodeficiency virus (HIV) increases the risk of acquiring human T-cell lymphotropic virus (HTLV) and subsequently HTLV's progression to tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). Existing data have exclusively reported generalized rates of HIV and HTLV-1 chronic viral infections in the Dominican Republic. To our knowledge, no published studies have focused on the rates of HTLV-1/2 in transactional sex workers and drug users, both higher risk groups, in the Dominican Republic. Methods From December 2012 to April 2013 we conducted a study to estimate the seroprevalence of HTLV-1/2 immunoglobulin G (IgG) and HIV antibodies among transactional sex workers and intravenous drug users in Santo Domingo, Dominican Republic. Serological status was analysed with behaviour and demographic data. Results We collected and analysed plasma from 200 participants with a mean age of 27.4 y in men and 25.2 y in women. The overall weighted seroprevalence of HTLV-1/2 IgG antibodies was 13.91% (95% CI 7.59 to 20.23) in men and 10.59% (95% CI 4.05 to 17.13) in women. The overall weighted seroprevalence of HIV-1 was 13.91% (95% CI 7.59 to 20.23%) in men and 17.65% (95% CI 9.55 to 25.75) in women. Male intravenous drug users had an exceptionally high rate of HTLV-positive HIV co-infection, at 75% (95% CI 44.99 to 105.01). Although there an association has been found between HTLV/HIV co-infections and sex work, the adjusted odds revealed a confounding role of HIV infection. Conclusions The results highlight the urgent need for enhanced public health preventive strategies among high-risk populations in the Dominican Republic and other resource-constrained Caribbean settings, as well as global adoption of routine screening for HTLV-associated infections, particularly in these high-risk, underserved populations.

BackgroundNatural killer (NK) cells are part of the innate immune system and provide surveillance against viruses and cancers. The ability of NK cells to kill virus-infected cells depends on the balance between the effects of inhibitory and activating NK cell receptors. This study aimed to investigate the phenotypic profile and the functional capacity of NK cells in the context of HTLV-1 infection.MethodsThis cross-sectional study sequentially recruited HTLV-1 infected individuals with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and asymptomatic HTLV-1 (AS) from the Integrated and Multidisciplinary HTLV Center in Salvador, Brazil. Blood samples from healthy blood donors served as controls. NK cell surface receptors (NKG2D, KIR2DL2/KIR2DL3, NKp30, NKG2A, NKp46, TIM-3 and PD-1), intracellular cytolytic (Granzyme B, perforin) and functional markers (CD107a for degranulation, IFN-) were assayed by flow cytometry in the presence or absence of standard K562 target cells. In addition, cytotoxicity assays were performed in the presence or absence of anti-NKp30.ResultsThe frequency of NKp30(+) NK cells was significantly decreased in HAM/TSP patients [58%, Interquartile Range (IQR) 30-61] compared to controls (73%, IQR 54-79, p=0.04). The production of cytolytic (perforin, granzyme B) and functional markers (CD107a and IFN-) was higher in unstimulated NK cells from HAM/TSP and AS patients compared to controls. By contrast, stimulation with K562 target cells did not alter the frequency of CD107a(+) NK cells in HAM/TSP subjects compared to the other groups. Blockage of the NKp30 receptor was shown to decrease cytotoxic activity (CD107a) and IFN- expression only in asymptomatic HTLV-1-infected individuals.ConclusionsNK cells from individuals with a diagnosis of HAM/TSP present decreased expression of the activating receptor NKp30, in addition to elevated degranulation activity that remained unaffected after blocking the NKp30 receptor.