LGL Leukemia and HTLV

Abstract

Samples were obtained from 53 large granular lymphocytic leukemia (LGLL) patients and 10,000 volunteer blood donors (VBD). Sera were screened in an HTLV-1 enzyme immunoassay (EIA) and further analyzed in peptide-specific Western blots (WB). DNAs were analyzed by HTLV-1, -2, -3, and -4-specific PCR. Forty four percent of LGLL patients vs. 0.12 % of VBD had anti-HTLV antibodies via EIA (p < 0.001). WB and PCR revealed that four LGLL patients (7.5%) vs. one VBD patient (0.01%) were infected with HTLV-2 (p < 0.001), suggesting an HTLV-2 etiology in a minority of cases. No LGLL patient was positive for HTLV-1, -3, or -4, whereas only one EIA-positive VBD was positive for HTLV-1 and none for HTLV-3 or -4. The HTLV EIA-positive, PCR-negative LGLL patients' sera reacted to epitopes within HTLV p24 gag and gp21 env. Other then the PTLV/BLV viruses, human endogenous retroviral element HERV K10 was the only sequence homologous to these two HTLV peptides, raising the possibility of cross-reactivity. Although three LGLL patients (5.7%) vs. none of 110 VBD patients tested positive for antibodies to the homologous HERV K10 peptide (p = 0.03), the significance of the anti-HTLV seroreactivity observed in many LGLL patients remains unclear. Interestingly, out of 36 HTLV-1-positive control subjects, 3 (8%) (p = 0.014) were positive for antibodies to HERV K10; all three had myelopathy. Out of 64 HTLV-2-positive control subjects 16 (25%) (p = <0.001) were positive for HERV K10 antibodies, and 4 (6%) of these had myelopathy. Out of 22 subjects with either HTLV-1 or -2 myelopathy, 7 (31.8%) were positive for HERV K10 antibodies, and out of 72 HTLV-infected subjects without myelopathy, 12 (16.7%) were positive for anti-HERV K10 antibodies (p = 0.11). The prevalence of anti-HERV K10 antibodies in these populations and the clinical implications thereof need to be pursued further.

HTLV infection among foreign pregnant women living in Spain

“…15 In samples with an indeterminate Western blot pattern, a new blood was drawn and peripheral blood mononuclear cells were obtained to perform genetic confirmation by polymerase chain reaction (PCR) and phylogenetic analyses, using primers and conditions reported elsewhere. 16 For the specific exclusion of HTLV-3 or HTLV-4 infections, primers specially designed for this purpose were used, as reported elsewhere. 17 Data from medical records were reviewed for subjects who were found to be HTLV-seropositive.…”

Human T-Cell Leukemia Virus Type 3 (HTLV-3) and HTLV-4 Antisense-Transcript-Encoded Proteins Interact and Transactivate Jun Family-Dependent Transcription via Their Atypical bZIP Motif

“…Whether antisense proteins are important for these different clinical outcomes in infected patients is an important issue. A limited number of individuals have been found to be infected by HTLV-3 or HTLV-4, and diseases have not yet been reported in these persons (14,15). Nonetheless, on the basis of our new results, it will be interesting to further investigate whether APH-3 or APH-4 could induce cell transformation or IL-2-independent T-cell growth.…”

Tumorigenesis related to retroviral infections

“…The primate T cell lymphoma/leukemia viruses (PTLV) comprise another oncogenenic genus of retroviruses, in which five human species have been identified: HTLV-1, -2, -3, -4, and -5 [29,30]. HTLV-1 retrovirus was first isolated in 1980 from peripheral blood of patients diagnosed with cutaneous T cell lymphoma and is considered the causative agent of T cell origin of leukemia/lymphoma present in adults and several chronic inflammatory diseases in the eyes, lungs, skeletal muscles, or central nervous system (HTLV-1 associated myelopathy/tropical spastic paraparesis: HAM/TSP) [20,31].…”

“…HTLV-3 and -4 have been discovered in Central Africa, whereas HTLV-5 has been reported in the past in a cutaneous T cell lymphoma case; however, the disease associations of all three viruses remain unconfirmed due to the limited number of cases in which they have been identified [20,29,30].…”