Compartmentalization and clonal amplification of HIV-1 variants in the cerebrospinal fluid during primary infection

J Virol. 2010 Mar;84(5):2395-407. doi: 10.1128/JVI.01863-09. Epub 2009 Dec 16.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Dementia Complex / cerebrospinal fluid*
  • AIDS Dementia Complex / genetics
  • AIDS Dementia Complex / physiopathology*
  • Amino Acid Sequence
  • Base Sequence
  • Central Nervous System / virology
  • Gene Amplification*
  • Genes, env
  • Genetic Variation
  • HIV Infections / blood
  • HIV Infections / cerebrospinal fluid*
  • HIV-1 / classification
  • HIV-1 / genetics*
  • HIV-1 / physiology*
  • Humans
  • Molecular Sequence Data
  • Phylogeny
  • Sequence Analysis, DNA
  • Virus Replication