Antiretroviral activity of 5-azacytidine during treatment of a HTLV-1 positive myelodysplastic syndrome with autoimmune manifestations

Abstract

Myelodysplastic syndromes (MDS) are often accompanied by autoimmune phenomena. The underlying mechanisms for these associations remain uncertain, although T cell activation seems to be important. Human T-lymphotropic virus (HTLV-1) has been detected in patients with myelodysplastic syndromes, mostly in regions of the world which are endemic for the virus, and where association of HTLV-1 with rheumatological manifestation is not rare. We present here the case of a 58 year old man who presented with cytopenias, leukocytoclastic vasculitis of the skin and glomerulopathy, and was diagnosed as MDS (refractory anemia with excess blasts - RAEB 1). The patient also tested positive for HTLV-1 by PCR. After 8 monthly cycles of 5-azacytidine he achieved a complete hematologic remission. Following treatment, a second PCR for HTLV-1 was carried out and found to be negative. This is the first report in the literature of a HTLV-1-positive MDS with severe autoimmune manifestations, which was treated with the hypomethylating factor 5-azacitidine, achieving cytogenetic remission with concomitant resolution of the autoimmune manifestations, as well as HTLV-1-PCR negativity. HTLV-1-PCR negativity may be due to either immune mediated clearance of the virus, or a potential antiretroviral effect of 5-azacytidine. 5-azacytidine is known for its antiretroviral effects, although there is no proof of its activity against HTLV-1 infection in vivo.

Analysis of Synonymous Codon Usage Bias of Zika Virus and Its Adaption to the Hosts

“…Previous studies found that dinucleotide compositional constraints of genomes can affect the codon usage bias [33]. Therefore, we determined the relative abundance of 16 dinucleotides in ZIKV polyprotein-coding regions.…”

“…Correspondence analysis (CA) is a useful multivariate statistical method for studying the internal relationship between variables and samples [33]. The mathematics procedure of CA transforms the RSCU values into a series of dimensional factors, and the results can be used to analyze the major trend in codon usage patterns among different samples.…”

Epigenetic Modification of the FoxP3 TSDR in HAM/TSP Decreases the Functional Suppression of Tregs

“…Many studies have utilized demethylating agents such as 5-aza-2′-deoxycytydine (DAC) and procainamide to demethylate the TSDR in Teffs, thereby transforming them into functionally suppressive Tregs (49, 50). Similar agents such as 5-azacytidine and valproate have been explored in HTLV-1 infection but only for their potential anti-retroviral and anti-leukemic properties (51, 52). To date, no one has explored their use in restoring Treg function in HAM/TSP.…”

Synergy and Order Effects of Antibiotics and Phages in Killing Pseudomonas aeruginosa Biofilms

“…One answer to this question brings us back a long past era and a therapy that has been virtually eclipsed by antibiotics, bacteriophage (phage) therapy. While there are clear limitations to the use of phage as the sole agent for treating bacterial infections [11, 12], it has been proposed that these bacterial viruses may be an effective adjunct to antibiotic treatment [13–15], and there is evidence in support of this proposition [16]. It has also been suggested that for ecological and physiological reasons, bacteriophage are likely to be more effective than antibiotics in killing bacteria within biofilms: (i) The polysaccharide depolymerase enzymes produced by phage are capable of breaking down the extracellular matrix of biofilms; antibiotics are not.…”