Central Nervous System Compartmentalization of HIV-1 Subtype C Variants Early and Late in Infection in Young Children

• DOI: 10.1371/journal.ppat.1003094
• Publication Date: 2013-01-02T17:37:06Z
• Authors: Christa Buckheit ...; Anna Dow; Cassandra B. Jabara; Sarah B. Joseph; Gretja Schnell; Nobutoki Takamune; Macpherson Mallewa; Robert S. Heyderman; Annelies Van Rie; Ronald Swanstrom
• Keywords: Tissue tropism; Compartmentalization (fire protection)

HIV-1 subtype B replication in the CNS can occur CD4+ T cells or macrophages/microglia adults. However, little is known about infection children ability of C to evolve macrophage-tropic variants. In this study, we examined variants ART-naïve aged three years younger determine viral genotypes and phenotypes associated with pediatric infection. We populations blood CSF 43 Malawian neurodevelopmental delay acute neurological symptoms. Using single genome amplification (SGA) phylogenetic analysis full-length env gene, defined four states: equilibrated virus (n = 20, 47%), intermediate compartmentalization 11, 25%), two distinct types compartmentalized 12, 28%). Older age a higher CSF/blood load ratio were compartmentalization, consistent independent CNS. Cell tropism was assessed using pseudotyped reporter viruses enter cell line on which CD4 CCR5 receptor expression be differentially induced. subset cases 2, 17%), able infect low surface expression, hallmark viruses, early an entry phenotype. Transmission multiple observed for 5 children; several cases, one variant sequestered within CNS, stochastic colonization by virus. Thus hypothesize pathways compartmentalization: sequestration transmitted from mother child, emergence later infection, average at 13.5 months, becoming fully apparent 18 months. Overall, occurred half year three.