Comparison of HIV-1 pol and env sequences of blood, CSF, brain and spleen isolates collected ante-mortem and post-mortem.
OBJECTIVE
HIV-1 infects the central nervous system (CNS) early in the course of infection. However, it is not known to what extent the virus evolves independently within the CNS and whether the HIV-RNA in cerebrospinal fluid (CSF) reflects the viral population replicating within the brain parenchyma or the systemic infection. The aim of this study was to investigate HIV-1 evolution in the CNS and the origin of HIV-1 in CSF.


METHODS
Longitudinally derived paired blood and CSF samples and post-mortem samples from CSF, brain and spleen were collected over a period of up to 63 months from three HIV-1 infected men receiving antiretroviral treatment and presenting with symptoms of AIDS dementia complex (ADC).


RESULTS
Phylogenetic analyses of HIV-1 V3, reverse transcriptase (RT) and protease sequences from patient isolates suggest compartmentalization with distinct viral strains in blood, CSF and brain. We found a different pattern of RT and accessory protease mutations in the systemic infection compared to the CNS.


CONCLUSIONS
We conclude that HIV-1 may to some extent evolve independently in the CNS and the viral population in CSF mainly reflects the infection in the brain parenchyma in patients with ADC. This is of importance in understanding HIV pathogenesis and can have implications on treatment of HIV-1 patients.
Caragounis
E-C
EC
Department of Clinical Virology, The Sahlgrenska Academy at Göteborg University, Gothenburg, Sweden.
Gisslén
M
M
Lindh
M
M
Nordborg
C
C
Westergren
S
S
Hagberg
L
L
Svennerholm
B
B
D000328:Adult; D001344:Autopsy / Q000379:methods; D015686:Gene Products, env / Q000378:metabolism*; D015684:Gene Products, pol / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism* / Q000473:pathology*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D012367:RNA, Viral / Q000097:blood; D017422:Sequence Analysis, DNA; D013154:Spleen / Q000378:metabolism* / Q000473:pathology / Q000821:virology
D015686:Gene Products, env; D015684:Gene Products, pol; D012367:RNA, Viral