Human T-lymphotropic Virus Type II Research Articles

Ultrasensitive fluorescent detection of HTLV-II DNA based on magnetic nanoparticles and atom transfer radical polymerization signal amplification

Human T-lymphotropic virus type II (HTLV-II) is a crucial retrovirus that is closely associated with a variety of human diseases. Herein, an ultrasensitive fluorescent HTLV-II DNA detection strategy was developed for the first time based on magnetic nanoparticles (MNPs) and atom transfer radical polymerization (ATRP) amplification. In this approach, hairpin DNA probes (pDNA) labelled with 5′ thiol and 3′ azide group terminally were immobilized on amino group modified MNPs surface through sulfo-N-succinimidyl-4-maleimidobutyrate sodium salt (sulfo-GMBS) cross-linkers. In the presence of target DNAs (tDNA), pDNA hybridized with tDNA to form double-stranded DNA, and therefore its azide group was away from the MNPs surface. Subsequently, to initiate ATRP reaction, initiators were introduced into the pDNA by a Cu (I)-catalyzed alkyne-azide cycloaddition (CuAAC). Then, large numbers of 9-anthracenylmethyl methacrylate polymer (pAMMA) were successfully labelled on the MNPs surface, resulting in significant amplification of the fluorescence signal. Under optimized conditions, the fluorescence signal was proportional to the logarithm of the concentration of tDNA over the range from 1 fM to 1 nM, with a detection limit of 0.22 fM. Moreover, this strategy was capable of discriminating mismatched bases and detecting HTLV-II DNA in human serum samples. By virtue of the high sensitivity, selectivity, simplicity and economy, this ultrasensitive biosensor demonstrates great potential for biomedical research and early clinical diagnosis.

Human T Lymphotropic Virus Type II Infection and Humoral Responses to Pneumococcal Polysaccharide and Tetanus Toxoid Vaccines

Infection with human T lymphotropic virus type II (HTLV-II) has been linked to an increased incidence of bacterial pneumonia. To determine whether HTLV-II infection is associated with impaired humoral immune responses, we immunized a cohort of HTLV-II-infected subjects and matched uninfected control subjects with 23-valent pneumococcal polysaccharide and tetanus toxoid vaccines. The pneumococcal polysaccharide vaccine elicited comparable and significant increases in concentrations of IgG against all 5 serotypes tested at 1 and 6 months after immunization in both groups. The avidity and opsonophagocytic functions of the anticapsular IgG were similar. The concentrations of tetanus toxoid-specific IgG also increased comparably and significantly over time in both groups. Thus, HTLV-II-infected persons develop robust humoral responses to potentially protective polysaccharide and protein vaccines.

Hepatitis C virus load and survival among injection drug users in the United States

Persons chronically infected with hepatitis C virus (HCV), some of whom may be coinfected with HIV and human T-lymphotropic virus type II (HTLV-II), are at high risk for end-stage liver disease (ESLD). We evaluated whether ESLD death was associated with premorbid HCV RNA level or specific HCV protein antibodies among persons with or without HIV/HTLV-II coinfection in a cohort of 6,570 injection drug users who enrolled in 9 US cities between 1987 and 1991. We compared 84 ESLD descendents and 305 randomly selected cohort participants with detectable HCV RNA, stratified by sex, race, HIV, and HTLV-II strata. Relative hazard (RH) of ESLD death was derived from the proportional hazard model. Risk of ESLD death was unrelated to the intensity of antibodies against the HCV c-22(p), c-33(p), c-100(p), and NS5 proteins, individually or combined, but it increased with HCV RNA level (RH(adj) = 2.26 per log(10) IU/mL, 95% CI: 1.45-5.92). The association between HCV RNA level and ESLD death remained significant after adjustment for alcohol consumption (RH(adj) = 2.57 per log(10) IU/mL, 95% CI: 1.50-8.10). Deaths from AIDS (n = 45) and other causes (n = 43) were unrelated to HCV RNA (RH(adj)= 1.14 and 1.29 per log(10) IU/mL, respectively). HIV infection was not associated with ESLD risk in multivariate analyses adjusted for HCV RNA. Men had an increased risk of ESLD death in unadjusted analyses (RH = 1.92, 95% CI: 1.15-3.56) but not in multivariate analysis (RH(adj) = 0.98, 95% CI: 0.48-2.88). Non-black patients were at increased risk for ESLD death (RH(adj)= 2.76, 95% CI: 1.49-10.09). In conclusion, HCV RNA level is a predictor of ESLD death among persons with chronic HCV infection.

Quantitation of HTLV-I and II proviral load using real-time quantitative PCR with SYBR Green chemistry

Human T-lymphotropic virus type I (HTLV-I) is linked etiologically with adult T cell leukemia/lymphoma and HTLV-I-associated myelopathy/tropical spastic paraparsis (HAM/TSP). Human T-lymphotropic virus type II (HTLV-II) is associated with HAM/TSP and, in HIV coinfected patients only, rare cases of cutaneous T cell lymphoma. Proviral load may be important in the pathogenesis of HTLV-associated disease. A real time quantitative PCR assay using SYBR Green intercalation was established. Primers targeting the tax region were standardized against MT2 and MOT cell line DNA for HTLV-I and HTLV-II, respectively. HTLV-I/II copy number was normalized to the amount of cellular DNA by quantitation of the HLA-DQ alpha gene. We measured proviral load in peripheral blood mononuclear cells (PBMCs) in a large cohort of 120 HTLV-I and 335 HTLV-II seropositive former blood donors. We also assessed the intra- and inter-assay reproducibility of the assay. Proviral load for HTLV-I infected patients ranged from 3.1 x 10(0) to 1.8 x 10(5)copies/10(6) PBMCs with a mean of 1.6 x 10(4) and a median of 3.0 x 10(3). HTLV-I was undetectable in 7 of 120 cases (5.8%). Proviral load for HTLV-II infected patients ranged from 1.1 x 10(0) to 1.0 x 10(6)copies/10(6) PBMCs with a mean of 2.8 x 10(4) and a median of 5.0 x 10(2). HTLV-II was undetectable in 31 out of 335 cases (9.3%). The assay has excellent dynamic range from 10(6) to 10(0)copies/reaction, good intra- and inter-assay reproducibility, and a lower limit of detection of a single copy per reaction. The sensitivity and high dynamic range allow determination of a broad range of HTLV-I/II proviral load in clinical subjects. This assay will facilitate the study of the relationship between proviral load and pathogenesis.

Comparison of CREB- and NF-κB-Mediated Transactivation by Human T Lymphotropic Virus Type II (HTLV-II) and Type I (HTLV-I) Tax Proteins

The function of the transactivator protein Tax from HTLV-II subtype A, subtype B, Brazilian subtype C, and African subtype D isolates was compared to that of Tax from an HTLV-I isolate. HTLV-II subtypes A, B, and C were less active in the transactivation of a NF-κB reporter compared to HTLV-I Tax in 293T but not Jurkat T cells. In both cell types there were no significant differences between the functions of HTLV-II B, C, and D and HTLV-I Tax proteins on either a full-length HTLV-I LTR or a 21-bp repeat reporter, suggesting that there is equivalent CREB-mediated transactivation between the viruses and these subtypes. In contrast, Tax of some but not all HTLV-II subtype A isolates, including the prototype Mo, had a greatly decreased ability to transactivate, and this could be directly correlated with a decrease in protein expression. Employment of cDNA clones encoding both Rex and Tax demonstrated that Rex was unable to rescue the expression or activity of the IIA Mo isolate. These studies demonstrate that with the exception of some HTLV-IIA subtypes there are no significant differences in Tax transactivation via the CREB and NF-κB pathways between the two viruses and suggest that the HTLV-II Tax may have a pathogenic potential equivalent to that of HTLV-I.

Cause-specific mortality associated with HIV and HTLV-II infections among injecting drug users in the USA

Human T-lymphotropic virus type II (HTLV-II) is widespread among injecting drug users (IDU) and may contribute to the risk of leukemia/lymphoma, neurodegenerative disease, and perhaps pneumonia, especially with HIV co-infection. In 1987--1991, 6570 IDU were tested for HIV and HTLV-II antibodies. In 1998, they were matched to the National Death Index. Numbers of observed deaths of each cause were compared by standardized mortality ratios with the numbers expected, using sex-, race-, age-, and year-specific rates in the general population. Relative risk (RR) associated with each virus, compared to uninfected drug users, was estimated by Poisson modeling. There were 1351 deaths, including 683 (15%) of 4604 participants who enrolled seronegative for both viruses; 328 (47%) of 701 who had HIV but not HTLV-II infection; 220 (21%) of 1033 who had HTLV-II but not HIV infection; and 120 (52%) of 232 who were infected by both viruses. Compared to the general population, mortality for participants with neither virus was increased 4.3-fold [95% confidence interval (CI), 4.0--4.7] and was significantly elevated for virtually every cause of death. With HIV, mortality from medical causes, but not external causes, was increased 3.7-fold (95% CI, 3.3--4.2), particularly with AIDS and related conditions. With HTLV-II, all-cause mortality was reduced (RR, 0.8; 95% CI, 0.7--0.9), with no statistically significant reduction or elevation for any specific cause. A non-significant excess of tuberculosis deaths (RR, 4.6; 95% CI, 0.8--25.2) was noted with HTLV-II, but there was no excess mortality from leukemia/lymphoma, other malignancies, or neurodegenerative disease. Without HIV or HTLV-II, IDU had profoundly increased mortality from medical and external causes. HIV was specifically associated with death due to AIDS and related conditions. HTLV-II infection was not significantly associated with mortality from any cause, suggesting that it is not a significant human pathogen, even when present with HIV infection.

Human T-Lymphotropic Virus Type II RFLP Subtypes a0 and b4/b5 are Associated with Different Demographic and Geographic Characteristics in the United States

Human T-lymphotropic virus type II (HTLV-II) prevalence is very low among the general U.S. population, intermediate among American Indians, and high among injecting drug users and their sexual partners. However, the transmission dynamics underlying this distribution are not well described. We obtained blood specimens from 493 blood donors found to be seropositive for HTLV-II at blood centers in five U.S. cities. Nested polymerase chain reaction was used to amplify a 672-bp region of the HTLV-II long terminal repeat region, and restriction fragment length polymorphism (RFLP) analysis was performed to classify each virus into subtypes as defined by Switzer et al. (1995, J. Virol. 69, 621–632). Associations between RFLP subtype and other characteristics were analyzed using multivariable logistic regression. HTLV-II subtype a0 was independently associated with age over 30 years (odds ratio (OR) = 2.12, 95% confidence interval (CI) 1.13–3.99) and with Black race/ethnicity (OR = 2.00, 95% CI 1.10–3.65 versus Hispanic race/ethnicity). Conversely, HTLV-II RFLP subtypes b4 and b5 were significantly more common among American Indian (OR = 3.77, 95% CI 1.23–11.57) and Other race/ethnicity (OR = 4.22, 95% CI 1.25–14.27, both versus Black race/ethnicity) and at the Oklahoma City blood center (OR = 3.57, 95% CI 1.08–11.84 compared to Washington, DC/Baltimore). There may have been at least two transmission foci of HTLV-II in the United States: a modest HTLV-II subtype a0 epidemic of unknown source in the 1960s and 1970s spread predominantly among Black persons in several geographic areas and a smaller focus of HTLV-II subtypes b4/b5 among non-Black individuals in Oklahoma and perhaps in other areas not examined by this study.

Spontaneous production of C-C chemokines by individuals infected with human T lymphotropic virus type II (HTLV-II) alone and HTLV-II/HIV-1 coinfected individuals.

To investigate the immunological features of human T lymphotropic virus type II (HTLV-II) infection and specific mechanisms whereby HTLV-II might influence the progression of HIV-1 disease in coinfected individuals, we have analyzed the production of the C-C chemokines RANTES and macrophage inflammatory proteins 1alpha and 1alpha (MIP-1alpha and MIP-1beta) by PBMCs from HTLV-II-infected and HTLV-II/HIV-1-coinfected individuals. We observed spontaneous production of significant levels of MIP-1alpha and -1beta and, to a lesser extent, RANTES, from individuals infected with HTLV-II alone or with concomitant HIV-1 infection. Spontaneous C-C chemokine production was not observed in PBMCs from uninfected or HIV-1-infected individuals. Although HTLV-II is known to preferentially infect CD8+ lymphocytes in vivo, we observed that whereas RANTES was produced exclusively by the CD8+-enriched fraction, MIP-1alpha and -1beta were produced by both the CD8+-enriched and CD8+-depleted fractions of HTLV-II-infected PBMCs. RT-PCR demonstrated active expression of the HTLV-II regulatory protein Tax in the infected CD8+ T lymphocyte population, and it was further shown that Tax transactivates the promoters of MIP-1beta and RANTES. Therefore, it appears that HTLV-II stimulates the production of C-C chemokines both directly at a transcriptional level via the viral transactivator Tax and also indirectly. Although the HTLV-II-infected individuals in this study are all virtually asymptomatic, they certainly display an abnormal immune phenotype. Moreover, our findings suggest that HTLV-II, via chemokine production, would be expected to alter the progression of HIV-1 infection in coinfected individuals.

Isolation, Cloning, and Complete Nucleotide Sequence of a Phenotypically Distinct Brazilian Isolate of Human T-Lymphotropic Virus Type II (HTLV-II)

Analysis of human T-lymphotropic virus type II (HTLV-II) isolates from North America and Europe have demonstrated the existence of two molecular subtypes of the virus, HTLV-IIa and HTLV-IIb. Recently, studies on HTLV-II infections in Brazil have revealed isolates that are related phylogenetically to the HTLV-IIa subtype but have a HTLV-IIb phenotype with respect to the transactivating protein, tax. To more clearly define this relationship, HTLV-II was isolated from peripheral blood of an IVDA from Sao Paulo, Brazil (SP-WV), and the complete provirus was cloned and sequenced. Comparison of HTLV-IISP-WV nucleotide sequences to other available complete HTLV-II proviral sequences revealed that HTLV-IISP-WV is most closely related to HTLV-IIMo, the prototypic HTLV-IIa subtype sequence. Phylogenetic analysis of LTR, env, and tax regions unequivocally demonstrated that HTLV-IISP-WV and all other Brazilian sequences examined are members of the IIa subtype. The predicted amino acid sequences of the major coding regions of HTLV-IISP-WV are also most closely related to HTLV-IIMo, with the important exception of tax. The tax protein encoded by HTLV-IISP-WV is 96–99% identical to the tax of IIb isolates and is similar in that it has an additional 25 amino acids at the carboxy-terminus compared to the HTLV-IIMo tax with which it shares 91% identity. Analysis of tax stop codon usage of a number of HTLV-IIa isolates from North American, Europe, and Brazil demonstrated that isolates from the last region appear to be unique in their extended tax phenotype. It could be demonstrated that the extended tax proteins in the HTLV-IIb and Brazilian isolates had equivalent ability to transactivate the viral LTR, and studies with deletion mutants indicated that the extended C-terminus is not essential for transactivation. In contrast, the HTLV-IIa tax was found to have a greatly diminished ability to transactivate the viral LTR, which appeared to be a consequence of reduced expression of the protein. The studies show that although the Brazilian strains do not represent an entirely new subtype based on nucleotide sequence analysis they are a phenotypically unique molecular variant within the HTLV-IIa subtype.

Sensitivity and specificity of human T-lymphotropic virus (HTLV) types I and II polymerase chain reaction and several serologic assays in screening a population with a high prevalence of HTLV-II.

Since 1988, all blood donations in the United States have been screened for antibodies to human T-lymphotropic virus type I (HTLV-I). However, the sensitivity of current serologic tests for the detection of HTLV type II (HTLV-II) antibodies and the diagnostic utility of direct tests for HTLV-I and -II using polymerase chain reaction (PCR) are poorly defined. Five hundred sixty-nine HTLV-I- or -II-seropositive and 687 age- and sex-matched seronegative samples from a high-risk population at an inner-city emergency department were selected. All samples were tested with four HTLV enzyme immunoassays (EIAs), one Western blot assay and one type-specific Western blot assay, one HTLV type-specific EIA, and a research HTLV-I/II PCR kit. Sensitivity of the various EIAs ranged from 95.1 to 99.5 percent, and specificity ranged from 97.2 to 99.4 percent. PCR performed in duplicate without selective retesting had lower sensitivity (85.1 %) and specificity (88.0%). However, PCR detected 20 (3.2%) HTLV-I-positive and 47 (7.5%) HTLV-II-positive samples among the 627 samples that were negative in all EIAs. The type-specific EIA and PCR assay had the highest rate of concordance in classifying samples as either HTLV-I or II, with the type-specific EIA and type-specific Western blot having the next highest rates of concordance. In this sample set from a population at high risk for HTLV-II, screening with HTLV-I/II PCR had lower sensitivity and specificity than that with EIAs. However, 4.1 to 10.8 percent of samples were PCR positive but seronegative for HTLV-I or -II, and their true infection status remains undetermined.

Increased incidence of infectious diseases during prospective follow-up of human T-lymphotropic virus type II- and I-infected blood donors. Retrovirus Epidemiology Donor Study.

To determine whether human T-lymphotropic virus type II (HTLV-II) infection is associated with an increased incidence of bacterial infections, we prospectively observed cohorts of HTLV-I- and HTLV-II-infected and seronegative subjects in 5 US cities. Of 1340 present and former blood donors examined at enrollment, 1213 (90.5%) were re-examined after approximately 2 years, including 136 HTLV-I- and 337 HTLV-II-seropositive subjects and 740 demographically stratified HTLV-seronegative subjects. All subjects were seronegative for human immunodeficiency virus. Odds ratios (ORs) for incident disease outcomes were adjusted for covariates, including age, sex, race or ethnicity, education, and, if significantly associated with the outcome, blood center, donation type, income, smoking, alcohol intake, and injected drug use. Compared with seronegative status, HTLV-II infection was associated with an increased incidence of bronchitis (OR, 1.81; 95% confidence interval [CI], 1.20-2.75), bladder and/or kidney infection (OR, 1.94; 95% CI, 1.26-2.98), oral herpes infection (OR, 9.54; 95% CI, 3.33-27.32), and a borderline increased incidence of pneumonia (OR, 2.09; 95% CI, 0.92-4.76); HTLV-I infection was associated with an increased incidence of bladder and/or kidney infection (OR, 2.79; 95% CI, 1.63-4.79). One incident case of HTLV-I-positive adult T-cell leukemia was observed (incidence, 348 per 100,000 HTLV-I person-years), and 1 case of HTLV-II-positive tropical spastic paraparesis-HTLV-associated myelopathy was diagnosed (incidence, 140 per 100,000 HTLV-II person-years). These data support an increased incidence of infectious diseases among otherwise healthy HTLV-II- and HTLV-I-infected subjects. They are also consistent with the lymphoproliferative effects of HTLV-I, and with neuropathic effects of HTLV-I and HTLV-II.

Establishment of monoclonal antibody, gp21-34, against HTLV-II envelope protein (p20E).

A monoclonal antibody (MAb), gp21-34, specifically reactive with human T-lymphotropic virus type-II (HTLV-II) transmembranous envelope glycoprotein (p20E) was developed by immunization with a recombinant protein fused with thioredoxin moiety at the N-terminal portion. This MAb, which belongs to the IgG1 kappa subclass, reacted with HTLV-II infected cell lines (TON-1, C3-44, and Si-IIA) by IFA, but not with HTLV-I infected cell lines (TCL-Kan and MT-2). By Western blot analysis, this MAb reacted with p20E of HTLV-II lysates but not with HTLV-I lysates. Some epitope analyses with synthetic peptides were carried out to look for a plausible linear epitope in the C-terminal region of p20E.

Molecular Epidemiology of HTLV-II among United States Blood Donors and Intravenous Drug Users: An Age–Cohort Effect for HTLV-II RFLP Type a0

Molecular subtyping was used to investigate the epidemiology of human T-lymphotropic virus type II (HTLV-II) in the United States. Nested polymerase chain reaction of the HTLV-II long terminal repeat region followed by restriction fragment length polymorphism (RFLP) analysis was performed on HTLV-II seropositive subjects including 97 U.S. blood donors without major risk factors for HTLV-II infection, 53 injection drug users (IDU), and 10 American Indian blood donors. Three new HTLV-II RFLP types were confirmed with DNA sequencing and phylogenetic analysis. HTLV-II RFLP type a0 (Switzer classification) was associated with older age [adjusted odds ratio (OR) 1.06 per year of age, 95% confidence interval (CI) 1.02–1.09] and with Black (OR 5.24, 95% CI 1.90–14.47) and White (OR 4.43, 95% CI 1.67–11.75) race/ ethnicity. These data are consistent with an age–cohort effect for HTLV-II RFLP type a0 among older White and Black IDU and blood donors. This finding could be explained by an epidemic of non-a0 HTLV-II RFLP types among younger persons of Hispanic and other race/ethnicity, superimposed upon endemic HTLV-II RFLP type a0 among older Black and White persons.

Nucleotide sequence variation of human T-lymphotropic virus type II in Vietnam.

A high rate of human T‐lymphotropic virus type II (HTLV‐II) infection has been documented in intravenous drug abusers (IVDAs) in South Vietnam. We have investigated the molecular characteristics of the virus and have shown that one HTLV‐II subtype is predominant in Ho Chi Minh City. This molecular subtype, HTLV‐IIb, was identified in a number of South Vietnamese by nucleotide sequence analysis of the long terminal repeat (LTR) region. HTLV‐IIa was not found. These findings suggest that HTLV‐IIb is endemic in IVDAs in South Vietnam, although IVDAs in urban areas in North America are predominantly infected with HTLV‐IIa.

Epidemiology of human T-lymphotropic virus type II (HTLV-II) infection in Spain. HTLV Spanish Study Group.

The human T-lymphotropic virus type II (HTLV-II) has recently been associated with the genesis of some subacute neurological syndromes and, rarely, with atypical T-lymphoid malignancies. The virus is endemic in some Amerindian and African tribes, and among intravenous drug users (IDUs) in North America and Europe. Given that HTLV-II is transmitted by the same routes as other human retroviruses, the screening of antibodies to HTLV-II in blood donors has became a matter of controversy in some countries. Herein, we describe the clinical, epidemiological and virological features of 113 individuals with HTLV-II infection identified in Spain up to September 1995. Most of them (94/113; 83%) were male, and all but seven were natives. Four were African immigrants living in Madrid and 3 had been born in other European countries. All but six subjects were IDUs, and sexual transmission of HTLV-II and transfusion were involved in five and one individual, respectively. Eighty-four percent of the IDUs infected with HTLV-II were co-infected by HIV-I (93/107). Clinical manifestations potentially linked to HTLV-II were absent, although an IDU male co-infected by HIV-1 and HTLV-II developed a severe non-inflammatory proximal myopathy. In conclusion, HTLV-II infection is present in Spain, mainly among IDUs, with a growing incidence and a current overall prevalence of 2.0 percent.

Highly endemic human T-lymphotropic virus type II (HTLV-II) infection in a Venezuelan Guahibo Amerindian group.

Sera from 166 Guahibo Indians (55% of the population) living in southwest Venezuela were screened by enzyme-linked immunoassay for antibodies to human T-cell lymphotropic virus (HTLV) I and II. Positive samples were confirmed by immunofluorescence and Western blot. Forty-one Guahibos (24.8%) were found to be seropositive. Polymerase chain reaction (PCR) analysis of proviral DNA in mononuclear cell lysates revealed the virus to be HTLV-II. Prevalence increased with age, and sexual contact with HTLV-II-seropositive partners was identified as a risk factor for infection. PCR amplification of a region of the pol gene, utilizing the primer pair SK110/SK111, with subsequent digestion of the 140-base-pair amplification products with HinfI and MseI restriction enzymes, showed an HTLV-II subtype-b restriction pattern in all cases. These data suggest that the substrain infecting this Guahibo community belongs to the b subtype, the most frequent among Paleo-Amerindian populations.

Genetic Variants of Human T-Lymphotropic Virus Type II in American Indian Groups

The human T-lymphotropic virus type II (HTLV-II) is found in many New World Indian groups in North and South America and may have entered the New World from Asia with the earliest migration of ancestral Amerindians over 15,000 years ago. To characterize the phylogenetic relationships of HTLV-II strains infecting geographically diverse Indian populations, we used polymerase chain reaction to amplify HTLV-II sequences from lymphocytes of seropositive Amerindians from Brazil (Kraho, Kayapo, and Kaxuyana), Panama (Guaymi), and the United States (the Navajo and Pueblo tribes of the southwestern states and the Seminoles of Florida). Sequence analysis of a 780-base pair fragment (located between theenvgene and the second exons oftax/rex) revealed that Amerindian viruses clustered in the same two genetic subtypes (IIa and IIb) previously identified for viruses from intravenous drug users. Most infected North and Central American Indians had subtype IIb, while HTLV-II infected members of three remote Amazonian tribes clustered as a distinct group within subtype IIa. These findings suggest that the ancestral Amerindians migrating to the New World brought at least two genetic subtypes, IIa and IIb. Because HTLV-II strains from Amazonian Indians form a distinct group within subtype HTLV-IIa, these Brazilian tribes are unlikely to be the source of IIa viruses in North American drug users. Finally, the near identity of viral sequences from geographically diverse populations indicate that HTLV-II is a very ancient virus of man.

Human T-lymphotropic virus type II in Japan.

Serum specimens were assayed for human T‐lymphotropic virus type II (HTLV‐II) infection in 1,500 individuals known to be seropositive for HTLV‐I and 30,000 blood donors in Japan. All HTLV‐I‐positive individuals were negative for HTLV‐II. However, one of the blood donors was clearly seropositive for HTLV‐II. Further, the donor was shown to be positive for HTLV‐IIb. Here we report at least one case with HTLV‐II in Japan and discuss the origin of the infection.

The clinical epidemiology of human T-lymphotropic virus type II (HTLV-II).

Human T-lymphotropic virus type II (HTLV-II) is endemic among Amerindian tribes and is also prevalent at high levels among certain U.S. and European intravenous drug users (IVDU), and at lower levels among blood donors. Most epidemiologic evidence supports transmission via parenteral, breast-feeding, and sexual routes, although more quantitative studies of the latter two routes are needed. There is growing evidence that HTLV-II causes a neurologic syndrome similar to HTLV-I-associated myelopathy, but there is some controversy as to whether the clinical features of this illness differ between HTLV-II and HTLV-I cases. Preliminary evidence also suggests that HTLV-II may predispose to skin and soft tissue bacterial infections among IVDU. Questions amenable to future research are discussed.

Human T lymphotropic virus type II (HTLV-II): epidemiology, molecular properties, and clinical features of infection.

Human T lymphotropic virus, type II (HTLV-II), infection has been shown to be endemic in a number of American Indian populations, and high rates of infection have also been documented in intravenous drug abusers in urban areas throughout the world. Although the role of HTLV-II in human disease has yet to be clearly defined, there is accumulating evidence that like HTLV-I, infection may also be associated with rare lymphoproliferative and neurological disorders. In this article we review and summarize the epidemiology, molecular properties and clinical features of HTLV-II infection.