Increased replication of non-syncytium-inducing HIV type 1 isolates in monocyte-derived macrophages is linked to advanced disease in infected children
Tuttle, D.L.; Anders, C.B.; Aquino-De Jesus, M.J.; Poole, P.P.; Lamers, S.L.; Briggs, D.R.; Pomeroy, S.M.; Alexander, L.; Peden, K.W.C.; Andiman, W.A.; Sleasman, J.W.; Goodenow, M.M.
Aids Research and Human Retroviruses 18(5): 353-362
2002
ISSN/ISBN: 0889-2229 PMID: 11897037 DOI: 10.1089/088922202753519133Document Number: 259664
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.