RESUMO
The role of CC chemokines in protection against mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission is not well understood. It was observed that mitogen-induced production of CCL3 and CCL4 by cord-blood mononuclear cells was increased among infants born to HIV-positive compared with HIV-negative mothers, and that a deficiency in production of CCL3 was associated with increased susceptibility to intrapartum HIV-1 infection. CCL3-L1 gene copy number was associated with CCL3 production and with vertical transmission. However, at equivalent CCL3-L1 gene copy numbers, infants who acquired HIV-1 infection relative to their exposed but uninfected counterparts had lower production of CCL3, suggesting that they may harbour some non-functional copies of this gene. Nucleotide changes that may influence CCL3 production were evident in the CCL3 and CCL3-L1 genes upstream of exon 2. Our findings suggest that infants who display a deficient-production phenotype of CCL3 are at increased risk of acquiring HIV-1, indicating that this chemokine in particular plays an essential role in protective immunity.
Assuntos
Quimiocinas CC/biossíntese , Infecções por HIV/imunologia , Infecções por HIV/transmissão , HIV-1 , Transmissão Vertical de Doenças Infecciosas , Sequência de Bases , Quimiocina CCL3 , Quimiocina CCL4 , Quimiocina CCL5 , Quimiocinas CC/sangue , Quimiocinas CC/genética , Estudos de Coortes , DNA/genética , Feminino , Sangue Fetal/imunologia , Dosagem de Genes , Soronegatividade para HIV/imunologia , Humanos , Técnicas In Vitro , Lactente , Recém-Nascido , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Proteínas Inflamatórias de Macrófagos/biossíntese , Proteínas Inflamatórias de Macrófagos/sangue , Mitógenos/farmacologia , Polimorfismo de Nucleotídeo Único , GravidezRESUMO
Phylogenetic relationships were examined for 29 southern African West Nile virus (formal name West Nile virus [WNV]) isolates from various sources in four countries from 1958 to 2001. In addition, sequence data were retrieved from GenBank for another 23 WNV isolates and Kunjin and Japanese encephalitis viruses. All isolates belonged to two lineages. Lineage 1 isolates were from central and North Africa, Europe, Israel, and North America; lineage 2 isolates were from central and southern Africa and Madagascar. No strict correlation existed between grouping and source of virus isolate, pathogenicity, geographic distribution, or year of isolation. Some southern African isolates have been associated with encephalitis in a human, a horse, and a dog and with fatal hepatitis in a human and death of an ostrich chick.