Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human immunodeficiency virus-1 (HIV-1) Vpr encodes a 14 kDa protein that has been implicated in viral pathogenesis through in vitro modulation of several host cell functions. Vpr modulates cellular proliferation, cell differentiation, apoptosis and host cell transcription in a manner that involves the glucocorticoid pathway. To better understand the role of HIV-1 Vpr in host gene expression, approximately 9600 cellular RNA transcripts were assessed for their modulation in primary APC after treatment with a bioactive recombinant Vpr (rVpr) by DNA micro-array. As an extracellular delivered protein, Vpr down-modulated the expression of several immunologically important molecules including CD40, CD80, CD83 and CD86 costimulatory molecules on MDM (monocyte-derived macrophage) and MDDC (monocyte-derived dendritic cells). Maturation of dendritic cells (DC) is known to result in a decreased capacity to produce HIV due to a post-entry block of the HIV-1 replicative cycle. Based on the changes observed in the gene array, we analyzed maturation of DC generated from monocytes in tissue culture as influenced by Vpr. We observed that Vpr-treated immature MDM and MDDC were unable to acquire high levels of costimulatory molecules and failed to develop into mature DC, even in the presence of maturation signals. These studies have importance for understanding the interaction of HIV with the host immune system.
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PMID:HIV-1 Vpr inhibits the maturation and activation of macrophages and dendritic cells in vitro. 1561 22

The HIV-1 vpr gene is conserved among the human (HIV-1, HIV-2) and simian immunodeficiency viruses (SIV). HIV-1 vpr encodes a 96-amino acid, 14 kDa protein (Vpr). Research from a number of laboratories in the last decade has shown that Vpr performs multiple functions, including the induction of cell cycle arrest in the G(2) phase, transactivation of the viral promoter, nuclear import of preintegration complexes, and induction of apoptosis in the infected cell. More recent studies have attempted to elucidate the cellular targets that Vpr utilizes in order to perform the above functions. This review presents the latest findings about the pathogenic events triggered by Vpr, the cellular pathways involved, and the molecular and cellular consequences of the action of Vpr in the context of HIV-1 infection.
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PMID:The role of Vpr in HIV-1 pathogenesis. 1563 22

The destruction of CD4(+) T cells and eventual induction of immunodeficiency is a hallmark of the human immunodeficiency virus type 1 infection (HIV-1). However, the mechanism of this destruction remains unresolved. Several auxiliary proteins have been proposed to play a role in this aspect of HIV pathogenesis including a 14 kDa protein named viral protein R (Vpr). Vpr has been implicated in the regulation of various cellular functions including apoptosis, cell cycle arrest, differentiation, and immune suppression. However, the mechanism(s) involved in Vpr-mediated apoptosis remains unresolved, and several proposed mechanisms for these effects are under investigation. In this review, we discuss the possibility that some of these proposed pathways might converge to modulate Vpr's behavior. Further, we also discuss caveats and future directions for investigation of the interesting biology of this HIV accessory gene.
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PMID:Human immunodeficiency virus type 1 (HIV-1) Vpr-regulated cell death: insights into mechanism. 1583 79

A line of research beginning in the early 1960s with the observation that West Nile virus and, later, several strains of rabies virus could inhibit the development of the Rous sarcoma virus-induced tumor in the wing-web of chicken (a "sarcoma-blockade") eventually culminated in the characterization of a 14-kDa circulating anti-sarcoma and anti-viral activity christened "plasma factor" (PF) which, unlike the interferons, inhibited the replication of diverse RNA-containing viruses, but not of any DNA-containing viruses. The possibility that this 14 kDa protein represented a novel antiviral cytokine has been strengthened by analysis of partial amino acid sequencing data which suggest that this 14-kDa cytokine may correspond to the 127-amino acid-long chicken YB2-like protein (Locus: XP_423576) deduced very recently from the genomic sequencing of chicken. Biologically, proteins of the Y-box family (such as chicken YB1 and YB2) not only bind DNA and thus regulate transcription but also bind single-stranded RNA in a sequence-specific and reversible manner, repress viral RNA translation, inhibit retroviral transformation of chicken fibroblasts, and are known to regulate transcription of human immunodeficiency virus and hepatitis B virus. Taken together, the available data point to a novel anti-viral cytokine with a novel mechanism of action.
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PMID:Is the anti-sarcoma and anti-viral cytokine "plasma factor" a novel chicken Y-box protein? 1713 7