Possible Biomarkers for the Early Detection of HIV-associated Heart Diseases: A Proteomics and Bioinformatics Prediction.

The frequency of cardiovascular disorders is increasing in HIV-infected individuals despite a significant reduction in the viral load by antiretroviral therapies (ART). Since the CD4 + T-cells are responsible for the viral load as well as immunological responses, we hypothesized that chronic HIV-infection of T-cells produces novel proteins/enzymes that cause cardiac dysfunctions. To identify specific factors that might cause cardiac disorders without the influence of numerous cofactors produced by other pathogenic microorganisms that co-inhabit most HIV-infected individuals, we analyzed genome-wide proteomes of a CD4 + T-cell line at different stages of HIV replication and cell growth over > 6 months.

Identification of human microRNA-like sequences embedded within the protein-encoding genes of the human immunodeficiency virus.

Background: MicroRNAs (miRNAs) are highly conserved, short (18-22 nts), non-coding RNA molecules that regulate gene expression by binding to the 3' untranslated regions (3'UTRs) of mRNAs. While numerous cellular microRNAs have been associated with the progression of various diseases including cancer, miRNAs associated with retroviruses have not been well characterized. Herein we report identification of microRNA-like sequences in coding regions of several HIV-1 genomes.

Proteomic characterization of HIV-modulated membrane receptors, kinases and signaling proteins involved in novel angiogenic pathways.

Background: Kaposi's sarcoma (KS), hemangioma, and other angioproliferative diseases are highly prevalent in HIV-infected individuals. While KS is etiologically linked to the human herpesvirus-8 (HHV8) infection, HIV-patients without HHV-8 and those infected with unrelated viruses also develop angiopathies. Further, HIV-Tat can activate protein-tyrosine-kinase (PTK-activity) of the vascular endothelial growth factor receptor involved in stimulating angiogenic processes.

HIV replication enhances production of free fatty acids, low density lipoproteins and many key proteins involved in lipid metabolism: a proteomics study.

Background: HIV-infected patients develop multiple metabolic abnormalities including insulin resistance, lipodystrophy and dyslipidemia. Although progression of these disorders has been associated with the use of various protease inhibitors and other antiretroviral drugs, HIV-infected individuals who have not received these treatments also develop lipid abnormalities albeit to a lesser extent. How HIV alters lipid metabolism in an infected cell and what molecular changes are affected through protein interaction pathways are not well-understood.

Inferring protein-protein interaction networks from protein complex data.

Present day approaches for the determination of protein-protein interaction networks are usually based on two hybrid experimental measurements. Here we consider a computational method that uses another type of experimental data: instead of direct information about protein-protein interactions, we consider data in the form of protein complexes. We propose a method for using these complexes to provide predictions of protein-protein interactions.

Molecular and phylogenetic analyses of a new amphotropic murine leukemia virus (MuLV-1313).

Background: The amphotropic murine leukemia viruses (MuLV-A's) are naturally occurring, exogenously acquired gammaretroviruses that are indigenous to the Southern California wild mice. These viruses replicate in a wide range of cell types including human cells in vitro and they can cause both hematological and neurological disorders in feral as well as in the inbred laboratory mice. Since MuLV-A's also exhibit discrete interference and neutralization properties, the envelope proteins of these viruses have been extremely useful for studying virus-host cell interactions and as vehicles for transfer of foreign genes into a variety of hosts including human cells.

Human immunodeficiency virus-associated disorders in Pakistan.

We have documented evidence of the human immunodeficiency virus (HIV) infection in four individuals including a blood donor and three members of a family (husband, wife, and a child) in Karachi, Pakistan. Our data indicate that HIV has been transmitted to the wife of the seropositive male, a drug abuser, in the recent past and that she has passed the virus to her newborn child perinatally/ transplacentally. The two seropositive males (blood donor and drug abuser) were diagnosed clinically as having persistent generalized lymphadenopathy, an AIDS-related condition (ARC), and the child presented with developmental disorders and neurologic manifestations.

Is Melanoma a stem cell tumor? Identification of neurogenic proteins in trans-differentiated cells.

BACKGROUND: Although several genes and proteins have been implicated in the development of melanomas, the molecular mechanisms involved in the development of these tumors are not well understood. To gain a better understanding of the relationship between the cell growth, tumorigenesis and differentiation, we have studied a highly malignant cat melanoma cell line that trans-differentiates into neuronal cells after exposure to a feline endogenous retrovirus RD114. METHODS: To define the repertoire of proteins responsible for the phenotypic differences between melanoma and its counterpart trans-differentiated neuronal cells we have applied proteomics technology and compared protein profiles of the two cell types and identified differentially expressed proteins by 2D-gel electrophoresis, image analyses and mass spectrometry.