Non-syncytium-inducing (NSI) strains of HIV-1 prevail among most infected children, including pediatric patients who develop advanced disease, severe immune suppression, and die. A study was designed to address the hypothesis that genotypic and/or phenotypic markers can distinguish NSI viruses isolated during early infection from NSI viruses found in advanced disease. Primary HIV-1 isolates, which were obtained from 43 children, adolescents, and adults who displayed a cross-section of clinical disease and immune suppression but were untreated by protease inhibitor antiretroviral therapy, were characterized for replication phenotype in different cell types. Most individuals (81%) harbored NSI viruses and almost half had progressed to advanced disease or severe immune deficiency. About 51% of NSI isolates produced low levels of p24 antigen (median, 142 pg/ml) in monocyte-derived macrophages (MDMs), 31% produced medium levels (median, 1584 pg/ml), and 17% produced high levels (median, 81,548 pg/ml) (p < 0.001). Seven of eight syncytium-inducing isolates also replicated in MDMs and displayed a dual-tropic phenotype that was associated with advanced disease. Replication of NSI viruses in MDMs varied as much as 100- to 1000-fold and was independent of replication in peripheral blood mononuclear cells. Replication in MDMs provided a clear biological feature to distinguish among viruses that were otherwise identical by NSI phenotype, V3 genotype, and CCR5 coreceptor usage. Low-level MDM replication was characteristic of viruses isolated from asymptomatic individuals, including long-term survivors. Enhanced MDM replication was related to morbidity and mortality among patients. Replication levels in MDMs provide a novel prognostic indicator of pathogenic potential by NSI viruses.
Leishmania parasites invade host macrophages, causing infections that are either limited to skin (cutaneous), or spread to internal organs (visceral). Macrophage-parasite interactions were investigated for three Leishmania species responsible for cutaneous leishmaniasis: L. major, L. aethiopica and L. tropica, using a monocyte cell line (THP-l). Fluorescence 2-D Difference Gel Electrophoresis (DIGE) was used and proteins differentially expressed during
infection were identified. Over 100 proteins showed significant changes of expression following infection with each of the three species tested. Proteins of interest were then separated, digested with trypsin and the peptide masses measured using MALDI-TOF. The identities of the proteins were elucidated by PMF. The identities and the involvement of the DE proteins will be discussed.
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