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

• DOI: 10.1371/journal.ppat.1004720
• Publication Date: 2015-03-27T17:16:46Z
• Authors: Christa Buckheit ...; Sarah B. Joseph; Gretja Schnell; Richard W. Price; Ronald Swanstrom; Serena Spudich
• Keywords: Adult; Central Nervous System; Male; 0301 basic medicine; AIDS Dementia Complex; QH301-705.5; Immunology; Virus Replication; Microbiology; Cell Line; 03 medical and health sciences; Clinical Research; Virology; 2.1 Biological and endogenous factors; 2.2 Factors relating to the physical environment; Humans; Viral; Aetiology; Biology (General); Biomedical and Clinical Sciences; Neurosciences; Medical microbiology; RC581-607; Middle Aged; 3. Good health; Viral Tropism; Mental Health; Infectious Diseases; Medical Microbiology; HIV-1; HIV/AIDS; Sexually Transmitted Infections; RNA; RNA, Viral; Female; Immunologic diseases. Allergy; Infection; Research Article

Compartmentalized HIV-1 replication within the central nervous system (CNS) likely provides a foundation for neurocognitive impairment and potentially important tissue reservoir. The timing of emergence character this local CNS has not been defined in population subjects. We examined frequency elevated cerebrospinal fluid (CSF) RNA concentration, nature CSF viral populations compared to blood, presence cellular inflammatory response (with potential bring infected cells into CNS) using paired blood samples obtained over first two years infection from 72 ART-naïve Using single genome amplification (SGA) phylodynamics analysis full-length env sequences, we 33 Independent (compartmentalization) was detected 20% sample pairs analyzed by SGA, or 7% all pairs, exclusively observed after four months infection. In subjects with longitudinal sampling, 30% showed evidence pleocytosis/inflammation at least one time point, approximately 16% evolving CSF/CNS compartmentalized and/or marked multiple points suggesting an ongoing recurrent impact CNS. Two had transmitted lineages (or their recombinant) largely sequestered shortly transmission, indicating additional mechanism establishing early replication. Transmitted variants were R5 T cell-tropic. Overall, examination relationships between populations, concentrations, responses suggested distinct states dynamics, associated mechanisms influx virus This study considerably enhances generalizability our results greatly expands knowledge interactions