Previous studies suggested that simian immunodeficiency viruses isolated from African green monkeys (SIVagm) are relatively nonpathogenic. The report describes the isolation and biologic and molecular characterization of a pathogenic SIVagm strain derived from a naturally infected African green monkey. This virus induced an AIDS-like syndrome characterized by early viremia, frequent thrombocytopenia, severe lymphoid depletion, opportunistic infections, meningoencephalitis, and death of five of eight macaques within 1 year after infection. An infectious clone derived from this isolate reproduced the immunodeficiency disease in pig-tailed (PT) macaques, providing definitive proof of the etiology of this syndrome. Although the virus was highly pathogenic in PT macaques, no disease was observed in experimentally infected rhesus macaques and African green monkeys despite reproducible infection of the last two species. Whereas infection of PT macaques was associated with a high viral load in plasma, peripheral blood mononuclear cells, and tissues, low-level viremia and infrequent expression in lymph nodes of rhesus macaques and African green monkeys suggest that differences in pathogenicity are associated with the extent of in vivo replication. The availability of a pathogenic molecular clone will provide a useful model for the study of viral and host factors that influence pathogenicity.

SUMMARYThe synthesis of the two respiratory syncytial (RS) virus glycoproteins (VP66 and VP84) was examined under standard conditions and after treatment with tunicamycin and monensin. The protein backbone for VP66, the fusion protein (F1,2) is cotranslationally glycosylated to form F0, which is cleaved to form F1, 2 by 20 min of chase. Monensin treatment inhibited the cleavage of Fo over an 80 min chase period, indicating that this occurred late in the transit of Fo through the Golgi apparatus or after exit from the Golgi apparatus. Tunicamycin treatment resulted in the synthesis of a 50K to 55K unglycosylated F0 which is cleaved to a 40K protein. VP84, the large glycoprotein, contains a protein backbone of only 26K to 30K which is modified by Nlinked and probable O-linked glycosylation. Tunicamycin treatment results in the synthesis of a 70K protein (p70) which incorporates [3H]glucosamine and [3H]fucose but not [3H]mannose. Glycosylated precursors varying in tool. wt. from 29K to 45K (p45) are found in infected cells at regular 2K to 3K intervals, producing a 'ladder' effect. The step from p45 to VP84 is severely delayed by monensin treatment thereby enhancing the 'ladder' effect of the precursors.

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Synthetic peptides, predicted from the nucleotide sequence of the S gene of hepatitis B virus were analyzed in terms of the established specificities of the hepatitis B surface antigen. The analysis indicated that the group-specific a antigen is composed of at least three nonoverlapping sequences and that a relatively hydrophilic region of the surface antigen protein, spanning amino acid residues 110-137, specifies the major d and y subtype system. The d/y subtype appears to depend on changes in one or more variable amino acids at positions 127, 131, and 134 of the hepatitis B surface antigen protein. Peptide 49 (consisting of amino acid sequences of the y subtype for the region 110-137), coupled to a carrier protein and mixed with an adjuvant, stimulated a brisk anti-y response in chimpanzees, the relevant model of human response to hepatitis B virus immunization and infection. Experimental challenge with homologous hepatitis B virus resulted in a pattern of partial protection. The results offer promise for the application of chemically synthesized peptides as vaccines in the prophylaxis of hepatitis B virus disease.Although a number of studies have suggested that the immunogenicity of a protein molecule depends largely on its conformation (1-3), more recent investigations have shown that reasonably short chemically synthesized peptides elicit antibodies reactive with virtually any region of an exposed surface of a protein (4). Coupled with the rapid determination of amino acid sequences via nucleic acid sequence analysis technology, synthetic peptides offer promise for vaccines that, in molecular terms, can be designed with a precision not heretofore possible.Hepatitis B virus (HBV) represents an important test model of the synthetic peptide vaccine approach. Current vaccines for HBV (5) consist of subviral components of the virus surface coat (HBsAg) purified from the plasma of chronically HBV-infected donors and inactivated. HBsAg has been the subject of extensive immunochemical characterization and consists of a groupspecific (a) and two sets of subtype-specific (d/y, w/r) determinants (6, 7); these specificities are associated with a single polypeptide (8, 9), the entire 226-amino acid sequence of which has been determined from the nucleotide sequence of the S gene (10) of It has been shown by radioimmunoprecipitation (15) and commercial solid-phase radioimmunoassays for anti-HBs (16) that antisera to synthetic peptides predicted from the nucleotide sequence of various regions of the S gene of HBV react with native HBsAg. We report here an analysis of the specificities of synthetic peptides in terms of the established HBsAg determinants and the immunogenicity of one such peptide in chimpanzees, the relevant human model of response. The data indicate that the group-specific (a). determinant is composed of at least three nonoverlapping sequences and that a relatively hydrophilic region of the HBsAg protein, residues 110-137 (numbered 1-226 from the amino terminus), specifies the major d/y subtype s...