Characterization of biological and immunological properties of human immunodeficiency virus type 1 (HIV-1) is critical to developing effective therapies and vaccines for AIDS. With the use of a novel CD4+ T-cell line (PM-1) permissive to infection by both monocytotropic (MT) and T-cell-tropic virus types, we present a comparative analysis of the immunological properties of a prototypic primary MT isolate of HIV-1 strain JR-CSF (MT-CSF) with those of a T-cell-tropic variant (T-CSF) of the same virus, which emerged spontaneously in vitro. The parental MT-CSF infected only PM-1 cells and was markedly resistant to neutralization by sera from HIV-1-infected individuals, rabbit antiserum to recombinant MT-CSF gpl20, and anti-V3 monoclonal antibodies. The T-CSF variant infected a variety of CD4+ T-cell lines, contained positively charged amino acid substitutions in the gpl20 V3 region, and was highly sensitive to antibody neutralization. Neutralization and antibody staining of T-CSF-expressing cells were significantly inhibited by HIV-1 V3 peptides; in contrast, the MT strain showed only weak V3-specific binding of polyclonal and monoclonal antibodies. Exposure of PM-1 cells to a mixture of both viruses in the presence of human anti-HIV-1 neutralizing antiserum resulted in infection with only MT-CSF. These results demonstrate that although the V3 region of MT viruses is immunogenic, the target epitopes in the V3 principal neutralizing domain on the membrane form of the MT envelope appear to be cryptic or hidden from blocking antibodies.

Mice from eight inbred strains were immunized with acetylcholine receptor (AChR) purified from Torpedo californica. All mice developed high concentrations of serum antibodies (10(-6) M) against the immunogen and approximately 80% possessed antibodies reactive with mouse nicotinic AChR. 33% of the mice immunized (n = 236) developed muscular weakness and flaccid paralysis. Behavioral, electrophysiological, and pharmacological similarities were found between the experimentally induced muscular weakness and the disease myasthenia gravis. Susceptibility to experimental myasthenia was found to be strain dependent in that the frequency of paralysis was much greater in some strains than others. The occurrence of muscular weakness and flaccid paralysis did not correlate with the concentration of antibodies reactive with T. californica or mouse AChR. Anti-receptor antibodies which increased the rate of AChR degradation on the mouse muscle cell line, BC3H-1, were found in the serum of both myasthenic and nonmyasthenic mice. 40% of the mice tested possessed antibodies reactive with antigenic determinants present on mouse receptor but not T. californica receptor. The occurrence of antibodies unique to mouse receptor did not correlate with myasthenia. Thus, myasthenia in the mouse does not occur simply as a consequence of the presence of antibodies directed against cell surface antigenic determinants of AChR. If anti-AChR antibodies are both necessary and sufficient for the induction of myasthenia, then these studies suggest that populations of a particular structure and/or specificity are required. It is anticipated that the mouse model of myasthenia gravis will permit the regulation of the anti-receptor immune response to be studied in detail.

Peripheral blood lymphocytes from chimpanzees infected for 3 months to more than 3 years with human immunodeficiency virus (HIV) had normal T-cell proliferative responses after stimulation with a variety of recall antigens and mitogens, indicating that HIV infection does not cause detectable immunological impairment in chimpanzees. This finding contrasts with that obtained in HIV-infected humans, who often have impaired T-cell reactivity. Peripheral blood lymphocytes from most HIV-infected chimpanzees that were studied also had strong proliferative responses to purified HIV as well as to HIV envelope glycoproteins isolated from the virus, to recombinant HIV envelope glycoproteins gpl20 and gp4l, and to HIV gag protein p24. The HIV-specific T-cell responses in HIV-infected chimpanzees may contribute to prevention of the development of acquired immunodeficiency syndrome in this species.

Human immunodeficiency virus type 1 (Z321 designate, HIV-1Z321), the oldest known HIV, was isolated from a serum sample collected in Zaire in 1976 and was molecularly cloned. Restriction enzyme analysis of unintegrated viral DNA revealed the presence of conserved restriction enzyme cleavage sites in the long terminal repeat sequences. Nucleotide sequence analysis of the 3' end of the viral DNA revealed a pattern similar to other HIV-1 isolates described. However, some of the common restriction sites present in other isolates were absent in HIV-1Z321. The extent of differences between HIV-1Z321 and recent isolates from North America and Zaire was 17.86-18.36% on the nucleotide sequence level and 26.5-33.2% difference in the predicted amino acid sequence in the envelope gene. Differences were also noted in 3'-orf (nef: according to HIV gene nomenclature; see Ref. 42) gene and U3 region of the long terminal repeat sequences of HIV-1Z321 and other isolates. Nucleotide sequence of a HIV-1 isolate, 12 years apart from the present isolates, will provide an important time calibration point for the evolutionary divergence of HIV isolates. Hybrid HIV was also generated by transfecting HIV-1Z321 and HIV-1HTLV-III viral DNAs into cells.

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