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.

Molecular studies have demonstrated the existence of at least two major subtypes of human T-cell lymphotropic virus type 2 (HTLV-2), designated HTLV-2a and HTLV-2b. To further investigate the heterogeneity of this family of viruses, we have characterized the HTLV-2 subtypes present in several urban areas in Brazil. DNAs from peripheral blood mononuclear cells of a large number of infected individuals, the majority of whom were intravenous drug abusers, were analyzed by using PCR with restriction fragment length polymorphism and nucleotide sequencing analysis. Restriction fragment length polymorphism analysis of the env region suggested that all individuals were infected with the HTLV-2a subtype, and this was confirmed by nucleotide sequence analysis. In contrast, nucleotide sequence analysis of the long terminal repeat demonstrated that although the viruses were more related to the HTLV-2a than to the HTLV-2b subtype, they clustered in a distinct phylogenetic group, suggesting that they may represent a new and distinct molecular subtype of HTLV-2. This conclusion was supported by nucleotide sequence analysis of the pX region, which demonstrated that the Tax proteins of the Brazilian viruses differed from that of prototype HTLV-2a isolates but were more similar to that of HTLV-2b in that they would be expected to have an additional 25 amino acids at the carboxy terminus. In transient expression assays, the extended Tax proteins were found to be much more potent transactivators of the virus long terminal repeat than the Tax protein of the prototype HTLV-2a subtype. The studies suggest that the Brazilian viruses analyzed in this study, while being phylogenetically related to the prototypic HTLV-2a seen in North America, are phenotypically more related to HTLV-2b and can be justifiably classified as a new molecular subtype, which has been tentatively designated HTLV-2c.

Prison populations are at increased risk of both human immunodeficiency virus (HIV) and Mycobacterium tuberculosis infections, but among female inmates information on such risks remains scarce, especially in developing countries. Between October 1992 and November 1993, 350 women incarcerated at a prison in São Paulo, Brazil, were prospectively evaluated for HIV and M. tuberculosis infection and disease. Among them, 87 (25%) were HIV seropositive, and 20 (5.7%) had tuberculosis (TB). During the incarceration period, the purified protein derivative test conversion rate was 29% for HIV-positive and 32% for HIV-negative women. However, the incidence of TB was 9.9 per 100 person-years for HIV-positive and 0.7 per 100 person-years of incarceration for HIV-negative women (p < 0.0001). A multivariate analysis indicated that HIV infection (p < 0.0001) and incarceration time < 12 months (p < 0.05) were each associated with TB. These findings indicate that new transmissions of M. tuberculosis infection are common among female inmates and that HIV-infected women are more likely to acquire active disease during the first 12 months of incarceration. Because of their role in childbearing and care female inmates are an important potential source of transmission of M. tuberculosis, and new strategies to control the spread of TB in prisons need to be developed.

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-II(SP-WV) nucleotide sequences to other available complete HTLV-II proviral sequences revealed that HTLV-II(SP-WV) is most closely related to HTLV-II(Mo), the prototypic HTLV-IIa subtype sequence. Phylogenetic analysis of LTR, env, and tax regions unequivocally demonstrated that HTLV-II(SP-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-II(SP-WV) are also most closely related to HTLV-II(Mo), with the important exception of tax. The tax protein encoded by HTLV-II(SP-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-II(Mo) 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.

Two hundred ninety-three individuals, who were enrolled in the HTLV out-clinic in Sao Paulo city, Brazil, between July 1997 and May 2003, were tested by EIAs, and positive sera 232 (79%) reactive by one of the tests. When these sera were tested by WB revealed 134 were HTLV-I, 28 HTLV-II, 4 HTLV-I/II, and 48 were indeterminate. Polymerase chain reaction (PCR) on the indeterminate group showed that 20 (42%) were HTLV-II and 28 were negative. From a total of 48 HTLV-II subjects with DNA available, restriction fragment length polymorphism (RFLP) of the env region revealed 47 HTLV-IIa and 1 HTLV-IIb. The phylogenetic analysis was performed on 23 samples, which identified 19 as subtype a, Brazilian subcluster, and 4 as subtype b. This is the first time HTLV-II subtype b has been described in Brazil. However, further studies, such as a complete nucleotide DNA sequencing, need to be done to confirm these findings.