Hematologic hints of HTLV-2 in US blood donors

The HOST investigators have maintained a multiregional and longitudinal survey of donors infected with HTLV-I and HTLV-II for over 14 years. The survey has provided extremely valuable information regarding the long-term consequences of asymptomatic infection with HTLV-I or HTLV-II.^1,2  In this issue of Blood, Bartman and colleagues demonstrate an association with abnormalities in hematologic parameters among HTLV-I and HTLV-II–infected blood donors through time, including elevations in hemoglobin, mean corpuscular volume, platelet counts, and absolute lymphocyte counts.

Human T-lymphotropic virus type II (HTLV-II), which has spread in epidemic proportions among injection drug users (IDUs) and their sexual partners, is often regarded as a virus without a disease. Nonetheless, with its more pathogenic counterpart, human T-lymphotropic virus type I (HTLV-I), it is a biologically important retrovirus that was transmitted by blood transfusion in the United States prior to the initiation of blood donor screening in 1988. Limited information exists regarding the long-term biologic and clinical outcomes of HTLV-II infection. Previous reports from the HTLV Outcomes Study (HOST) have linked HTLV-II infection with increased morbidity/mortality, an increased risk for pneumonia and bronchitis, urinary tract infections, and rare neurologic manifestations.²  Recently, HTLV-II coinfection was associated with an observable survival benefit and delay in progression to AIDS among HIV-1–infected IDUs.³ 

While HTLV-I has been definitively proven to cause adult T-cell leukemia/lymphoma and a progressive neurodegenerative illness known as tropical spastic paraparesis/HTLV-I–associated myelopathy (TSP/HAM), a causal role for HTLV-II with either leukemia or TSP/HAM is much less well-defined and based on a handful of case reports. Long-term asymptomatic HTLV-II infection has been identified in American Indians, a group in which the virus is thought to have existed for hundreds or perhaps thousands of years with little evolutionary change.⁴ 

In the absence of clinical disease, Bartman et al observed clear alterations in the hematologic parameters of HTLV-II–infected blood donors over time. The reasons for these findings are unclear. While HTLV-I has primary tropism for CD4⁺ T cells, HTLV-II may share differential tropism with both CD4⁺ and CD8⁺ T cells.⁵  In the present study, preliminary analysis of lymphocyte subpopulations failed to reveal any strong associations, but it is anticipated that further immunophenotypic and molecular/genetic analysis of lymphocytes from the patient population could prove fruitful in understanding the biologic basis for the clinical findings.

There are plausible explanations on a biologic level that explain the findings of Bartman et al. The transcriptional activating proteins of HTLV-I and HTLV-II, known as Tax1 and Tax2, are essential for viral replication but also modulate several key host cellular genes, such as cytokines and their receptors, antiviral chemokines, transcription factors (such as c-fos, c-sis, c-rel, c-myc, and others), proapoptotic factors, DNA repair enzymes, cell cycling pathways, growth factors, and adhesion molecules.⁶ 

While the clinical consequences of HTLV-II infection remain infrequent and poorly studied, counseling and treatment of the HTLV-II–infected individual remains problematic. Confusion exists among professionals and lay people alike as to the significance of a positive HTLV-II blood testing result in the face of asymptomatic infection. Referral to an experienced hematologist or infectious disease specialist for further clinical evaluation of these patients often results in unnecessary tests and increased anxiety on the part of the affected person. Therefore, the knowledge gained from long-term observational studies, such as that published by Bartman et al, is invaluable in helping clinicians and subspecialists understand the more subtle hematologic abnormalities of chronic infection with this human retrovirus.