Compartmentalization and clonal amplification of HIV-1 variants in the cerebrospinal fluid during primary infection.
Human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) is a severe neurological disease that affects a subset of HIV-1-infected individuals. Increased compartmentalization has been reported between blood and cerebrospinal fluid (CSF) HIV-1 populations in subjects with HAD, but it is still not known when compartmentalization arises during the course of infection. To assess HIV-1 genetic compartmentalization early during infection, we compared HIV-1 populations in the peripheral blood and CSF in 11 primary infection subjects, with analysis of longitudinal samples over the first 18 months for a subset of subjects. We used heteroduplex tracking assays targeting the variable regions of env and single-genome amplification and sequence analysis of the full-length env gene to identify CSF-compartmentalized variants and to examine viral genotypes within the compartmentalized populations. For most subjects, HIV-1 populations were equilibrated between the blood and CSF compartments. However, compartmentalized HIV-1 populations were detected in the CSF of three primary infection subjects, and longitudinal analysis of one subject revealed that compartmentalization during primary HIV-1 infection was resolved. Clonal amplification of specific HIV-1 variants was identified in the CSF population of one primary infection subject. Our data show that compartmentalization can occur in the central nervous system (CNS) of subjects in primary HIV-1 infection in part through persistence of the putative transmitted parental variant or via viral genetic adaptation to the CNS environment. The presence of distinct HIV-1 populations in the CSF indicates that independent HIV-1 replication can occur in the CNS, even early after HIV-1 transmission.
Schnell
Gretja
G
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, North Carolina 27599-7295, USA.
Price
Richard W
RW
Swanstrom
Ronald
R
Spudich
Serena
S
D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid* / Q000235:genetics / Q000503:physiopathology*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002490:Central Nervous System / Q000821:virology; D005784:Gene Amplification; D015752:Genes, env; D014644:Genetic Variation; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D014779:Virus Replication