Human immunodeficiency virus-1 evolutionary patterns associated with pathogenic processes in the brain.
The interplay between pathology and human immunodeficiency virus (HIV) expansion in brain tissues has not been thoroughly assessed in the highly active antiretroviral therapy (HAART) era. HIV-associated dementia (HAD) is marked by progressive brain infection due to recruitment and migration of macrophages in brain tissues; however, the cellular and viral events occurring prior to HAD development and death are under debate. In this study, 66 brain tissues from 11 autopsies were analyzed to assess HIV-1 DNA concentration in brain tissues. In most patients without HAD, it was impossible to amplify HIV-1 from brain tissues. Amplifiable DNA was obtained from three cases of patients on HAART who died due to primary pathology other than HAD: (1) cardiovascular disease, a disease associated with HAART therapy; (2) bacterial infections, including Mycobacterium avium complex, rapid occurrence of extreme dementia; and (3) acquired immunodeficiency syndrome (AIDS)-related lymphoma with meningeal involvement. HIV-1 DNA was also amplified from multiple tissues of two HAD patients. Analysis of HIV-1 nef, gp120, and gp41 sequences showed reduced viral evolution within brain tissues for the non-HAD cases relative to patients with clinical and histological HAD. The present study is the first to show a potential correlation between HIV-1 evolutionary patterns in the brain and different neuropathologies.
Lamers
Susanna L
SL
BioInfoExperts, Thibodaux, Louisiana, USA.
Salemi
Marco
M
Galligan
Derek C
DC
Morris
Alanna
A
Gray
Rebecca
R
Fogel
Gary
G
Zhao
Li
L
McGrath
Michael S
MS
D015526:AIDS Dementia Complex / Q000188:drug therapy / Q000473:pathology* / Q000821:virology*; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D023241:Antiretroviral Therapy, Highly Active; D050197:Atherosclerosis / Q000473:pathology; D001499:Bayes Theorem; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology; D016384:Consensus Sequence; D018450:Disease Progression; D019143:Evolution, Molecular; D016655:HIV Core Protein p24 / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015700:HIV Envelope Protein gp41 / Q000235:genetics; D015497:HIV-1 / Q000235:genetics*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics*; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008969:Molecular Sequence Data; D010802:Phylogeny; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D054298:Human Immunodeficiency Virus Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C514793:gp120 protein, Human immunodeficiency virus 1; C514837:nef protein, Human immunodeficiency virus 1; C514799:p24 protein, Human Immunodeficiency Virus Type 1