Compartmentalized Replication of R5 T Cell-Tropic HIV-1 in the Central Nervous System Early in the Course of Infection


Early HIV-1 CNS replication likely provides a foundation for brain injury and a potentially important tissue reservoir. To explore the character and timing of emergence of early HIV-1 CNS replication, we examined paired cerebrospinal fluid (CSF) and blood samples from 72 ART-naïve adults, with one-half having longitudinal samples, during the first two years following HIV-1 subtype B infection. In a cross sectional analysis over the first two years of infection, 10–25% of subjects had evidence of either local viral replication in the CNS, defined by the presence of CSF compartmentalization, or a robust inflammatory response, and in approximately 16% of subjects this CNS involvement persisted over time. In some subjects, one of two transmitted viruses replicated predominantly within the CNS, providing insight into how HIV-1 can establish independently replicating populations early in different parts of the body. Based on their entry phenotype, all viruses were selected for replication in CD4+ T cells, although this phenotype was slightly altered in the compartmentalized virus. Overall, we suggest four states to model the nature of HIV-1 CNS infection, which imply distinct mechanisms of virus/host interaction within the CNS during early infection.


Vyšlo v časopise: Compartmentalized Replication of R5 T Cell-Tropic HIV-1 in the Central Nervous System Early in the Course of Infection. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004720
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004720

Souhrn

Early HIV-1 CNS replication likely provides a foundation for brain injury and a potentially important tissue reservoir. To explore the character and timing of emergence of early HIV-1 CNS replication, we examined paired cerebrospinal fluid (CSF) and blood samples from 72 ART-naïve adults, with one-half having longitudinal samples, during the first two years following HIV-1 subtype B infection. In a cross sectional analysis over the first two years of infection, 10–25% of subjects had evidence of either local viral replication in the CNS, defined by the presence of CSF compartmentalization, or a robust inflammatory response, and in approximately 16% of subjects this CNS involvement persisted over time. In some subjects, one of two transmitted viruses replicated predominantly within the CNS, providing insight into how HIV-1 can establish independently replicating populations early in different parts of the body. Based on their entry phenotype, all viruses were selected for replication in CD4+ T cells, although this phenotype was slightly altered in the compartmentalized virus. Overall, we suggest four states to model the nature of HIV-1 CNS infection, which imply distinct mechanisms of virus/host interaction within the CNS during early infection.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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