Proteomic analyses of monocyte-derived macrophages infected with human immunodeficiency virus type 1 primary isolates from Hispanic women with and without cognitive impairment.
Submitted by Loyda Milagros Melendez, Ph.D. on
Title | Proteomic analyses of monocyte-derived macrophages infected with human immunodeficiency virus type 1 primary isolates from Hispanic women with and without cognitive impairment. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Toro-Nieves, DM, Rodriguez, Y, Plaud, M, Ciborowski, P, Duan, F, J Laspiur, P, Wojna, V, Meléndez, LM |
Journal | J Neurovirol |
Volume | 15 |
Issue | 1 |
Pagination | 36-50 |
Date Published | 2009 Jan |
ISSN | 1538-2443 |
Keywords | AIDS Dementia Complex, Cells, Cultured, Cognition, Cognition Disorders, Electrophoresis, Polyacrylamide Gel, Enzyme-Linked Immunosorbent Assay, Female, Hispanic Americans, HIV Infections, HIV-1, Humans, Macrophages, Proteome, Proteomics, Tandem Mass Spectrometry, Virulence, Virus Replication |
Abstract | The signature for human immunodeficiency virus type 1 (HIV-1) neurovirulence remains a subject of intense debate. Macrophage viral tropism is one prerequisite but others, including virus-induced alterations in innate and adaptive immunity, remain under investigation. HIV-1-infected mononuclear phagocytes (MPs; perivascular macrophages and microglia) secrete toxins that affect neurons. The authors hypothesize that neurovirulent HIV-1 variants affect the MP proteome by inducing a signature of neurotoxic proteins and thus affect cognitive function. To test this hypothesis, HIV-1 isolates obtained from peripheral blood of women with normal cognition (NC) were compared to isolates obtained from women with cognitive impairment (CI) and to the laboratory adapted SF162, a spinal fluid R5 isolate from a patient with HIV-1-associated dementia. HIV-1 isolates were used to infect monocyte-derived macrophages (MDMs) and infection monitored by secreted HIV-1 p24 by enzyme-linked immunosorbent assay (ELISA). Cell lysates of uninfected and HIV-1-infected MDMs at 14 days post infection were fractionated by cationic exchange chromatography and analyzed by surface enhanced laser desorption ionization time of flight (SELDI-TOF) using generalized estimating equations statistics. Proteins were separated by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (1D SDS-PAGE) and identified by tandem mass spectrometry. Levels of viral replication were similar amongst the HIV-1 isolates, although higher levels were obtained from one viral strain obtained from a patient with CI. Significant differences were found in protein profiles between virus-infected MDMs with NC, CI, and SF162 isolates (adjusted P value after multiple testing corrections, or q value <.10). The authors identified 6 unique proteins in NC, 7 in SF162, and 20 in CI. Three proteins were common to SF162 and CI strains. The MDM proteins linked to infection with CI strains were related to apoptosis, chemotaxis, inflammation, and redox metabolism. These findings support the hypothesis that the macrophage proteome differ when infected with viral isolates of women with and without CI. |
DOI | 10.1080/13550280802385505 |
Alternate Journal | J. Neurovirol. |
PubMed ID | 19115125 |
PubMed Central ID | PMC2947716 |
Grant List | G12 RR003051 / RR / NCRR NIH HHS / United States G12 RR003051-23 / RR / NCRR NIH HHS / United States G12 RR003051-245425 / RR / NCRR NIH HHS / United States GM 061838 / GM / NIGMS NIH HHS / United States P20 RR 11126 / RR / NCRR NIH HHS / United States P20 RR011126-14 / RR / NCRR NIH HHS / United States R25 GM061838 / GM / NIGMS NIH HHS / United States R25 GM061838-09 / GM / NIGMS NIH HHS / United States RR 03051 / RR / NCRR NIH HHS / United States S06 GM 0822 / GM / NIGMS NIH HHS / United States S06 GM008224 / GM / NIGMS NIH HHS / United States S06 GM008224-19 / GM / NIGMS NIH HHS / United States U54 NS 430 / NS / NINDS NIH HHS / United States U54 NS043011 / NS / NINDS NIH HHS / United States U54 NS043011-01 / NS / NINDS NIH HHS / United States U54 NS043011-07 / NS / NINDS NIH HHS / United States |