The genetic subtypes of human immunodeficiency virus type 1 (HIV-1) display differences in immunologie reactivity1 and possibly transmissibility.2 In addition to the high replication rate of HIV-1 and the infidelity of its reverse transcriptase, interstrain recombination may increase the diversity of phenotypes this virus generates. The discoveries that more than 10% of the HIV-1 strains sequenced to date are intersubtype recombinant3 and that the subtype E viruses prevalent in Thailand are probably subtype A/E recombinant4,5 suggest that recombination between viruses belonging to distinct subtypes occurs to an appreciable extent and that the resulting recombinant progeny are transmissible.Cross-immunity between HIV-1 antigens with divergent primary sequences has been a desired goal of preventive and therapeutic vaccine design. Here we report our finding that the Zairian strain used to make an inactivated, gpl20-depleted, therapeutic HIV-1 immunogen6,7 is subtype G/subtype A recombinant. This strain, Z321, was isolated from a previously frozen serum sample taken in 1976 from a 26-year-old Zairian woman who died of an AIDS-like illness in 1978.8 The virus was propagated initially in peripheral blood lymphocytes (PBLs) and later in the transformed T cell line HUT 78 for the purpose of manufacturing the therapeutic immunogen. We amplified (by polymerase chain reaction [PCR]) short segments of the Z321 provirus in DNA extracted from Z321 (passage 6 of vaccine productionj-infected CEM 3 and HUT 78 cells (Fig. 1). Amplified products were subcloned and recombinant DNA templates sequenced as described elsewhere.9 Phylogenetic analysis (PHYLIP 3.5) of individual PCR clones revealed a significant association of gag clones for subtype G ( 11 of 11 ) and env clones for subtype A (12 of 17 by method 1, 11 of 17 by method 2; see Fig. 1) (p < 0.001, Fisher exact test). This result raised the question as to whether distinct subtype G and A viruses or recombinational hybrid viruses existed in our Z321-infected cell cultures. Recombination between subtype A and G target sequences during PCR is unlikely to explain our result since this phenomenon would be expected to result in A/G mosaicism within a minority of the PCR products in any one amplification and would therefore not be expected to skew gag clones to G and env clones to A. Because the sequences of most of the PCR primers used were derived from the subtype B isolate HIV-1sf2> preferential amplification efficiency of our gag primers for subtype G sequences and our env primers for subtype A sequences is also unlikely. This was confirmed by theoretical measures of primability and stability of primer matches for consensus A and consensus G targets (Amplify 1.2 computer program, data not shown). All multiple clones derived from any particular amplicon were for the most part identical, and in a few cases nearly identical. Because of the multiple short segments amplified and sequenced, these considerations make more likely the presence of an intersubtype recombinant virus rather t...
The primate T-cell lymphoma/leukemia viruses belong to an oncogenic genus of complex retroviruses. Members of this genus have been shown to be pathogenic in man. The human T-cell lymphoma/leukemia virus (HTLV) type I has been linked in the etiology of T-cell malignancies and "autoimmune-like" neurologic and rheumatic disorders; a related virus, HTLV-II, is becoming increasingly associated with similar disorders. Cell transformation is thought to be caused predominantly by the effects of the viral regulatory protein, Tax. An additional induced host cell molecule, adult T-cell lymphoma-derived factor, may contribute to cell immortalization. Like the DNA tumor viruses, HTLV activates transcription of cellular proto-oncogenes and inhibits cellular mechanisms of tumor suppression, cell cycle arrest, and apoptosis. However, individuals who are able to mount a strong cell-mediated immune response and limit viral entry into uninfected cells do not develop associated malignancies. Unfortunately, HTLV-induced malignancies are difficult to treat with conventional chemotherapy, and disease progression is often rapid with a median survival of less than 2 years. There are, however, some novel approaches that have yet to be fully tested that may have greater efficacy in the treatment of HTLV-induced diseases. In the future, better screening and detection methods, along with new vaccines and therapies, may contribute to the increased prevention and control of HTLV infection and its associated diseases.
There were no significant differences among the sensitivities and specificities of the HTLV-I/II ELISAs (p values, 0.056-0.438). The WB and PCR assays were much more specific than the other serologic assays (p=0.03). However, the PCR assay is significantly (p<0.001) more sensitive than any of the serologic assays in the detection of HTLV-II infection. Thus, optimal detection of HTLV-II infection would seem to require both serologic and DNA PCR assays.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.