Human immunodeficiency virus-1 evolutionary patterns associated with pathogenic processes in the brain

• Published in: Journal of neurovirology 2010-06, Vol.16 (3), p.230-241
• Main Authors: Lamers, Susanna L, Salemi, Marco, Galligan, Derek C, Morris, Alanna, Gray, Rebecca, Fogel, Gary, Zhao, Li, McGrath, Michael S
• Format: Article
• Language: English
• Subjects: AIDS Dementia Complex - drug therapy; AIDS Dementia Complex - pathology; AIDS Dementia Complex - virology; Amino Acid Sequence; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Antiretroviral Therapy, Highly Active; Atherosclerosis - pathology; Autopsy; Bayes Theorem; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Brain; Brain - metabolism; Brain - pathology; Brain - virology; Cardiovascular diseases; Consensus Sequence; Dementia disorders; Disease Progression; DNA; Evolution; Evolution, Molecular; Glycoprotein gp120; glycoprotein gp41; highly active antiretroviral therapy; HIV Core Protein p24 - metabolism; HIV Envelope Protein gp120 - genetics; HIV Envelope Protein gp41 - genetics; HIV-1 - genetics; Human immunodeficiency virus 1; Human Immunodeficiency Virus Proteins - genetics; Human viral diseases; Humans; Immunodeficiency; Immunology; Infection; Infectious Diseases; Leukocyte migration; Lymphoma; Macrophages; Macrophages - metabolism; Macrophages - pathology; Macrophages - virology; Medical sciences; Molecular Sequence Data; Mycobacterium avium; nef Gene Products, Human Immunodeficiency Virus - genetics; Nef protein; Neurology; Neuropathology; Neurosciences; Phylogeny; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral diseases of the nervous system; Virology
• ISSN: 1355-0284; 1538-2443
• DOI: 10.3109/13550281003735709

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.