In cats, infection with T-lymphotropic retroviruses can cause T-cell proliferation and leukemia or T-cell depletion and immunosuppression. In humans, some highly T4 tropic retroviruses called HTLV-I can cause T-cell proliferation and leukemia. The subgroup HTLV-II also induces T-cell proliferation in vitro, but its role in disease is unclear. Viruses of a third subgroup of human T-lymphotropic retroviruses, collectively designated HTLV-III, have been isolated from cultured cells of 48 patients with acquired immunodeficiency syndrome (AIDS). The biological properties of HTLV-III and immunological analyses of its proteins show that this virus is a member of the HTLV family, and that it is more closely related to HTLV-II than to HTLV-I. Serum samples from 88 percent of patients with AIDS and from 79 percent of homosexual men with signs and symptoms that frequently precede AIDS, but from less than 1 percent of heterosexual subjects, have antibodies reactive against antigens of HTLV-III. The major immune reactivity appears to be directed against p41, the presumed envelope antigen of the virus.

Microbial superantigens (SAGs) have been implicated in the pathogenesis of human autoimmune diseases. Preferential expansion of the Vveta7 T cell receptor positive T cell subset in patients suffering from acute-onset type I diabetes has indicated the presence of a surface membrane-bound SAG. Here, we have isolated a novel mouse mammary tumor virus-related human endogenous retrovirus. We further show that the N-terminal moiety of the envelope gene encodes an MHC class II-dependent SAG. We propose that expression of this SAG, induced in extrapancreatic and professional antigen-presenting cells, leads to beta-cell destruction via the systemic activation of autoreactive T cells. The SAG encoded by this novel retrovirus thus constitutes a candidate autoimmune gene in type I diabetes.

We performed a phylogenetic analysis of caprine and ovine lentiviruses using long sequences in gag and pol of 104 new Swiss isolates and six available corresponding database sequences. Forty-five isolates, forming five sequence clusters, were unclassifiable by the present classification. Pairwise DNA distance analysis indicated different categories of relatedness, requiring a new classification system. We propose four principal sequence groups, A-D, which differ by 25-37%. Groups A and B are further divided into subtypes which differ by 15-27%. Group D and four of the seven group A subtypes, A3, A4, A5 and A7, are formed by new Swiss isolates. Molecular epidemiology revealed that Swiss B1 strains differed no more from French, Brazilian or US strains than from each other, suggesting virus propagation through international livestock trade. Furthermore, infection of goats by subtypes A3 or A4 was significantly associated with documented contact with sheep, which also harbor these subtypes, thus indicating regularly occurring sheep-to-goat transmission.

The two main subgroups of the family of human T-lymphotropic retroviruses (HTLV) that have previously been characterized are known as HTLV-I and HTLV-II. Both are associated with certain human leukemias and lymphomas. Cell surface antigens (p61 and p65) encoded by HTLV-I are frequently recognized, at low titers, by antibodies in the serum of patients with acquired immunodeficiency syndrome (AIDS) or with signs or symptoms that precede AIDS (pre-AIDS). This suggests an involvement of HTLV in these disorders. Another subgroup of HTLV, designated HTLV-III, has now been isolated from many patients with AIDS and pre-AIDS. In the studies described in this report, virus-associated antigens in T-cell clones permanently producing HTLV-III were subjected to biochemical and immunological analyses. Antigens of HTLV-III, specifically detected by antibodies in serum from AIDS or pre-AIDS patients and revealed by the Western blot technique, are similar in size to those found in other subgroups of HTLV. They include at least three serologically unrelated antigenic groups, one of which is associated with group-specific antigens (p55 and P24) and another with envelope-related (p65) proteins, while the antigens in the third group are of unknown affiliation. The data show that HTLV-III is clearly distinguishable from HTLV-I and HTLV-II but is also significantly related to both viruses. HTLV-III is thus a true member of the HTLV family.

Reverse transcriptase (RT) is an indispensable component of infectious retroviruses. We have developed an ultrasensitive RT test in which RNA of bacteriophage MS2 serves as the template for RT-mediated cDNA synthesis. A fragment of the cDNA is selectively amplified by polymerase chain reaction and the amplication product is analyzed by Southern blot hybridization or enzyme immunoassay. The procedure was 10'6 to 107 times more sensitive than a conventional RT test and detected as little as 10-9 unit of murine leukemia virus RT, which corresponded to 2.1 X 102 molecules, a number present in 3-11 virions. As a screening assay for filterable particle-associated RT, it was positive with supernatants from cell cultures producing human immunodeficiency virus (11V) type 1 or human T-cell leukemia virus (fITLV) type 1 or 2, but was negative with nonproducer cultures. It was positive with plasma samples from all tested individuals infected with HIV-1, HIV-2, or HTLV-1 and sera from cats infected with feline leukemia virus or feline immunodeficiency virus. Control samples from blood donors or uninfected cats were negative. Density banding experiments with culture supernatants showed that the RT activity was associated with virus particles. The assay should detect all replicationcompetent retroviruses or similar agents. It may be used as a screening assay for such agents, for quantitation of the viral load, drug susceptibility testing of RT, and control of virus inactivation in biological products.Infectious retroviruses are important causative agents of human and animal disease. They all possess a characteristic enzyme, reverse transcriptase (RT), and can thus be detected by assays for this activity (1,2). However, the current tests are insensitive when compared with virus-specific methods. Detection of human immunodeficiency virus type 1 (HIV-1) by RT assay, for example, is 100 times less sensitive than by antigen (Ag) assay (3). Polymerase chain reaction (PCR) is again orders of magnitude more sensitive (4).The narrow detection range of sequence-based tests such as PCR is, however, a disadvantage when detection of retroviruses in general is the aim. Attempts to detect uncharacterized retroviruses by the use of PCR with primers from conserved genomic regions have been met with some success but lack sensitivity and, therefore, require prior isolation and multiplication of the virus in a suitable host cell line usually difficult to find (5). Here, we report the development of an ultrasensitive RT assay capable of detecting retroviruses at a sensitivity hitherto reserved to virus-specific sequence amplification.tained from R. C. Gallo (National Institutes of Health, Bethesda, MD). HTLV-IIIB was also produced in C81-66-45 (hence called C81-66-45/HIV-1). The HTLV-1 producer MT-2 was from I. Miyoshi (Kochi Medical School, Kochi, Japan), the cloned HTLV-2 producer 76D9 was from J. Jendis (our laboratory), and the uninfected monocytoid cell line RC2A was from P. Stoeckbauer (Center Sample Pretreatment. One milliliter o...