Detection of antibodies to human T-cell leukemia virus types 1 and 2 in breast milk from East Asian women.

We investigated the incidence of human T-cell leukemia virus type I (HTLV-1) infection in a total of 17 regions in four countries, including 13 regions in Japan, as well as Korea (Seoul and Busan), China, and Vietnam, by testing breast milk using a particle agglutination assay (PA) and line immunoassay (LIA). Among 266 samples from Japan, 24 (9.0%) were positive on PA and 3 (1.1%) were positive on LIA. Among 50 samples from Seoul, 2 were positive on PA and 1 was positive on LIA. In contrast, all 50 samples from Busan were negative on both tests, suggesting the maldistribution of HTLV-1 infectants in South Korea. The numbers of positive samples were 2/91 on PA and 1/91 on LIA for China and 1/88 on both PA and LIA for Vietnam. In China, one sample with a high probability of HTLV-2 infection was identified by LIA and synthetic peptide enzyme-linked immunosorbent assay (ELISA). We examined HTLV-1 antibody in breast milk samples using commercially available test kits, suggesting the existence of HTLV-1 carriers in endemic areas in Southeast Asia and an HTLV-2 infectant in China. As a part of human ethno-epidemiological research, these results constitute valuable epidemiological data. Further studies on the sensitivity, specificity, and reliability of assays using antibodies to HTLV-1 and 2 in breast milk will be necessary for large-scale epidemiological surveys of HTLV infection.

Screening for antibodies to human T-cell leukemia virus type I in Japanese breast milk.

Japanese breast milk samples were tested for antibodies to human T-cell leukemia virus type I (HTLV-1) by particle agglutination (PA) and a line immunoassay (LIA). In the PA method, the agglutination reaction between the HTLV-1 antibody and sensitized particles occurred at a 1 : 128 dilution of some breast milk samples. The average antibody titer was one order of magnitude lower than that in the serum positive control. A total of 243 human breast milk specimens were assayed by PA, of which 21 samples from Okinawa, Hyogo, Miyagi and Hokkaido were positive or deferred. The results of the 21 positive samples were subsequently assayed by LIA (INNO-LIA™ HTLV I/II) for confirmation; and one sample was positive, and two were indeterminate. We attempted to use polymerase chain reaction (PCR) to detect HTLV-1 provirus DNA, but we did not detect PCR products for the pX1 region of the HTLV-1 genome in the LIA-positive samples. These negative PCR results are most likely due to the lower sensitivity of the PCR for amplification from milk than from HTLV-1-positive monocytes. In conclusion, the PA method to breast milk samples appears to be a suitable tool to screen for antibodies to HTLV-1 in the breast milk of carrier mothers in cases in which it would be difficult to use serum for the test. Although LIA may be able to confirm HTLV-1 infection, the presence of HTLV-1 provirus should be confirmed in the breast milk.

Low frequency of human T-cell lymphotropic virus 1 antibodies in Iranian gastric cancer patients in comparison to controls.

There is some evidence that human T-cell lymphotropic virus (HTLV-1) infection has a reverse association with gastric cancer (GC). Data about this association in the Iranian population are scarce. In this study we therefore assessed the frequency of anti-HTLV-1 antibody in GC patients and compare it to antibody presence in healthy individuals in Iranian population. This case control study was performed between 2008-2011 on 201 GC patients and 219 control subjects. HTLV-1 antibodies were assessed by ELISA and the positive results were confirmed by western blotting. Totals of 201 gastric cancer patients and 219 controls were enrolled in this study. The tumors in the majority of patients (45.3%) were in the distal (non-cardia) area. Mean age of patients at the time of diagnosis was 59.2±12.5 and mean age of controls was 57.7±11.3. While only one GC patient (0.5%) was positive for HTLV-1 antibody, there were four individuals (1.89%) from the control group with antibodies. In addition, smoking had statistically significant relationship with cancer (P=0.001). Our study showed that the frequency of HTLV-1 antibody in patients was lower than in controls, similar to the results obtained in Japan. Further investigations with a larger sample size are needed in order to determine the association between GC and HTLV-1 infection in Iran.

Conformation-specific antibodies targeting the trimer-of-hairpins motif of the human T-cell leukemia virus type 1 transmembrane glycoprotein recognize the viral envelope but fail to neutralize viral entry.

Human T-cell leukemia virus type 1 (HTLV-1) entry into cells is dependent upon the viral envelope glycoprotein-catalyzed fusion of the viral and cellular membranes. Following receptor activation of the envelope, the transmembrane glycoprotein (TM) is thought to undergo a series of fusogenic conformational transitions through a rod-like prehairpin intermediate to a compact trimer-of-hairpins structure. Importantly, synthetic peptides that interfere with the conformational changes of TM are potent inhibitors of membrane fusion and HTLV-1 entry, suggesting that TM is a valid target for antiviral therapy. To assess the utility of TM as a vaccine target and to explore further the function of TM in HTLV-1 pathogenesis, we have begun to examine the immunological properties of TM. Here we demonstrate that a recombinant trimer-of-hairpins form of the TM ectodomain is strongly immunogenic. Monoclonal antibodies raised against the TM immunogen specifically bind to trimeric forms of TM, including structures thought to be important for membrane fusion. Importantly, these antibodies recognize the envelope on virally infected cells but, surprisingly, fail to neutralize envelope-mediated membrane fusion or infection by pseudotyped viral particles. Our data imply that, even in the absence of overt membrane fusion, there are multiple forms of TM on virally infected cells and that some of these display fusion-associated structures. Finally, we demonstrate that many of the antibodies possess the ability to recruit complement to TM, suggesting that envelope-derived immunogens capable of eliciting a combination of neutralizing and complement-fixing antibodies would be of value as subunit vaccines for intervention in HTLV infections.

Chronic active VZV infection manifesting as zoster sine herpete, zoster paresis and myelopathy.

After lumbar-distribution zoster, an HTLV-1-seropositive woman developed chronic radicular sacral-distribution pain (zoster sine herpete), cervical-distribution zoster paresis and thoracic-distribution myelopathy. Detection of anti-varicella zoster virus (VZV) IgM and VZV IgG antibody in cerebrospinal fluid (CSF), with reduced serum/CSF ratios of anti-VZV IgG compared to normal serum/CSF ratios for albumin and total IgG, proved that VZV caused the protracted neurological complications. Diagnosis by antibody testing led to aggressive antiviral treatment and a favorable outcome.

Expression of CD23, CD32, Mac-1 and other adhesion molecules in eosinophils in strongyloidiasis and HTLV-I-positive patients.

The relationship between human T-lymphotropic virus I (HTLV-I) infection and strongyloidiasis has recently become an important problem. This study compared the expression of CD23, CD32, Mac-1 and other adhesion molecules in eosinophils of patients with strongyloidiasis positive for anti-(HTLV-I) antibodies and in those negative for the antibodies. The expression of CD23, Mac-1 and intercellular adhesion molecule-1 (ICAM-1) on eosinophils of patients with strongyloidiasis was augmented in comparison with normal subjects and HTLV-I carriers. There were no significant differences, however, in the expression of CD23, CD32, Mac-1 and adhesion molecules (ICAM-1, leukocyte function-associated antigen-1 alpha (LFA-1 alpha), LFA-1 beta, very late antigen-4) on eosinophils of patients with strongyloidiasis positive for anti-HTLV-I antibodies in comparison with those negative for these antibodies.

Immunological studies in tropical spastic paraparesis.

Tropical spastic paraparesis (TSP) and other chronic-progressive myelopathies have been clearly associated with increased serum and cerebrospinal fluid antibody titers to human T-lymphotropic virus type I (HTLV-I). However, little is known about the cellular immune function in TSP. In the present study, activated T lymphocytes were found in the peripheral blood of patients with TSP. Specifically, there were increased numbers of large CD3+ cells that also expressed HLA-DR and interleukin-2-receptor molecules. A significantly elevated spontaneous lymphoproliferative response was demonstrated in all patients tested. Generation of measles virus-specific cytotoxic T-cell response was reduced in 4 of 4 patients. This was similar to previous findings in patients with multiple sclerosis. However, unlike multiple sclerosis, reduced generation of cytotoxic T-cell response to influenza and mumps viruses was observed in 2 of 4 patients. These observations confirm further the strong association between TSP and an HTLV-I-like virus and suggest that the observed abnormalities of the cellular immune response in TSP are related to infection of lymphocytes by the retrovirus.

HTLV-I-associated myelopathy and adult T-cell leukemia cases in a family.

Familial cases of HTLV-I-associated myelopathy (HAM) and adult T-cell leukemia (ATL), developing in a daughter and father, respectively, are reported. The coexistence of both diseases in a family has not been reported before. This supports the recent findings that ATL and HAM may be brought about by an identical virus on an apparently different immunogenetic background.