Abstract
BackgroundHIV-1 R5 viruses are characterized by a large phenotypic variation, that is reflected by the mode of coreceptor use. The ability of R5 HIV-1 to infect target cells expressing chimeric receptors between CCR5 and CXCR4 (R5broad viruses), was shown to correlate with disease stage in HIV-1 infected adults. Here, we ask the question whether phenotypic variation of R5 viruses could play a role also in mother-to-child transmission (MTCT) of HIV-1 and pediatric disease progression.Methodology/Principal FindingsViral isolates obtained from a total of 59 HIV-1 seropositive women (24 transmitting and 35 non transmitting) and 28 infected newborn children, were used to infect U87.CD4 cells expressing wild type or six different CCR5/CXCR4 chimeric receptors. HIV-1 isolates obtained from newborn infants had predominantly R5narrow phenotype (n = 20), but R5broad and R5X4 viruses were also found in seven and one case, respectively. The presence of R5broad and R5X4 phenotypes correlated significantly with a severe decline of the CD4+ T cells (CDC stage 3) or death within 2 years of age. Forty-three percent of the maternal R5 isolates displayed an R5broad phenotype, however, the presence of the R5broad virus was not predictive for MTCT of HIV-1. Of interest, while only 1 of 5 mothers with an R5X4 virus transmitted the dualtropic virus, 5 of 6 mothers carrying R5broad viruses transmitted viruses with a similar broad chimeric coreceptor usage. Thus, the maternal R5broad phenotype was largely preserved during transmission and could be predictive of the phenotype of the newborn's viral variant.Conclusions/SignificanceOur results show that R5broad viruses are not hampered in transmission. When transmitted, immunological failure occurs earlier than in children infected with HIV-1 of R5narrow phenotype. We believe that this finding is of utmost relevance for therapeutic interventions in pediatric HIV-1 infection.
Highlights
Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) is the primary mode of infection in children
In 14 out of 16 children tested the infection was possibly acquired during the intrapartum period, since negative results were obtained by polymerase chain reaction (PCR) within the first week of life
CXCR4 using virus was isolated from one newborn only, confirming previous observations that CCR5 is preferentially used by HIV-1 early after infection [3]
Summary
Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) is the primary mode of infection in children. Viruses using CXCR4 as coreceptor (X4 phenotype) can be transmitted when present in the mother, CCR5-using viruses (R5 phenotype) are the most frequently detected in newborns [3,4]. Evolution of HIV-1 coreceptor use during disease progression has been demonstrated in adults as well as children [5,6]. HIV-1 R5 viruses are characterized by a large phenotypic variation, that is reflected by the mode of coreceptor use. The ability of R5 HIV-1 to infect target cells expressing chimeric receptors between CCR5 and CXCR4 (R5broad viruses), was shown to correlate with disease stage in HIV-1 infected adults. We ask the question whether phenotypic variation of R5 viruses could play a role in mother-to-child transmission (MTCT) of HIV-1 and pediatric disease progression
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