Macrophages and CD4؉ lymphocytes are the principal target cells for human immunodeficiency virus type 1 (HIV-1) infection, but the molecular details of infection may differ between these cell types. During studies to identify cellular molecules that could be involved in macrophage infection, we observed inhibition of HIV-1 infection of macrophages by monoclonal antibody (MAb) to the tetraspan transmembrane glycoprotein CD63. Pretreatment of primary macrophages with anti-CD63 MAb, but not MAbs to other macrophage cell surface tetraspanins (CD9, CD81, and CD82), was shown to inhibit infection by several R5 and dualtropic strains, but not by X4 isolates. The block to productive infection was postfusion, as assessed by macrophage cell-cell fusion assays, but was prior to reverse transcription, as determined by quantitative PCR assay for new viral DNA formation. The inhibitory effects of anti-CD63 in primary macrophages could not be explained by changes in the levels of CD4, CCR5, or -chemokines. Infections of peripheral blood lymphocytes and certain cell lines were unaffected by treatment with anti-CD63, suggesting that the role of CD63 in HIV-1 infection may be specific for macrophages.
The structure of recombinant domain III of the envelope protein (rED3) of yellow fever virus (YFV), containing the major neutralization site, was determined using NMR spectroscopy. The amino acid sequence and structure of the YFV-rED3 shows differences from ED3s of other mosquito-borne flaviviruses; in particular, the partially surface-exposed BC loop where methionine-304 and valine-324 were identified as being critical for the structure of the loop. Variations in the structure and surface chemistry of ED3 between flaviviruses affect neutralization sites and may affect host cell receptor interactions and play a role in the observed variations in viral pathogenesis and tissue tropism.
Yellow fever virus (YFV), a reemerging disease agent in Africa and South America, is the prototype member of the genus Flavivirus. Based on examination of the prM/M, E and 39 non-coding regions of the YFV genome, previous studies have identified seven genotypes of YFV, including the Angolan, east/central African and east African genotypes, which are highly divergent from the prototype strain Asibi. In this study, full genome analysis was used to expand upon these genetic relationships as well as on the very limited full genome database for YFV. This study was the first to investigate genomic sequences of YFV strains from east and central Africa (Angola71, Uganda48a and Ethiopia61b). All three viruses had genomes of 10 823 nt in length. Compared with the prototype strain Asibi (from west Africa) they were approximately 25 % divergent in nucleotide sequence and 7 % divergent in amino acid sequence. Comparison of multiple flaviviruses in the N-terminal region of NS4B showed that amino acid sequences were variable and that west African strains of YFV had an amino acid deletion at residue 21. Additionally, N-linked glycosylation sites were conserved between viral genotypes, while codon usage varied between strains.
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