Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We showed previously that during the HIV/AIDS epidemic, the envelope glycoprotein (Env) of HIV-1, and in particular, the gp120 subunit, evolved toward an increased resistance to neutralizing antibodies at a population level. Here, we considered whether the antigenic evolution of the HIV-1 Env is associated with modifications of its functional properties, focusing on cell entry efficacy and interactions with the receptor and coreceptors. We tested the infectivity of a panel of Env-pseudotyped viruses derived from patients infected by subtype B viruses at three periods of the epidemic (1987 to 1991, 1996 to 2000, and 2006 to 2010). Pseudotyped viruses harboring Env from patients infected during the most recent period were approximately 10-fold more infectious in cell culture than those from patients infected at the beginning of the epidemic. This was associated with faster viral entry kinetics: contemporary viruses entered target cells approximately twice as fast as historical viruses. Contemporary viruses were also twice as resistant as historical viruses to the fusion inhibitor enfuvirtide. Resistance to enfuvirtide correlated with a resistance to CCR5 antagonists, suggesting that contemporary viruses expanded their CCR5 usage efficiency. Viruses were equally captured by DC-SIGN, but after binding to DC-SIGN, contemporary viruses infected target cells more efficiently than historical viruses. Thus, we report evidence that the infectious properties of the envelope glycoprotein of HIV-1 increased during the course of the epidemic. It is plausible that these changes affected viral fitness during the transmission process and might have contributed to an increasing virulence of HIV-1.IMPORTANCE Following primary infection by HIV-1, neutralizing antibodies (NAbs) exert selective pressure on the HIV-1 envelope glycoprotein (Env), driving the evolution of the viral population. Previous studies suggested that, as a consequence, Env has evolved at the HIV species level since the start of the epidemic so as to display greater resistance to NAbs. Here, we investigated whether the antigenic evolution of the HIV-1 Env is associated with modifications of its functional properties, focusing on cell entry efficacy and interactions with the receptor and coreceptors. Our data provide evidence that the infectious properties of the HIV-1 Env increased during the course of the epidemic. These changes may have contributed to increasing virulence of HIV-1 and an optimization of transmission between individuals.
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PMID:Evolution of the Envelope Glycoprotein of HIV-1 Clade B toward Higher Infectious Properties over the Course of the Epidemic. 3056 94

Human Immunodeficiency Virus (HIV) infects cells from the immune system and has thus developed tools to circumvent the host immunity and use it in its advance. Dendritic cells (DCs) are the first immune cells to encounter the HIV, and being the main antigen (Ag) presenting cells, they link the innate and the adaptive immune responses. While DCs work to promote an efficient immune response and halt the infection, HIV-1 has ways to take advantage of their role and uses DCs to gain faster and more efficient access to CD4+ T cells. Due to their ability to activate a specific immune response, DCs are promising candidates to achieve the functional cure of HIV-1 infection, but knowing the molecular partakers that determine the relationship between virus and cell is the key for the rational and successful design of a DC-based therapy. In this review, we summarize the current state of knowledge on how both DC subsets (myeloid and plasmacytoid DCs) act in presence of HIV-1, and focus on different pathways that the virus can take after binding to DC. First, we explore the consequences of HIV-1 recognition by each receptor on DCs, including CD4 and DC-SIGN. Second, we look at cellular mechanisms that prevent productive infection and weapons that turn cellular defense into a Trojan horse that hides the virus all the way to T cell. Finally, we discuss the possible outcomes of DC-T cell contact.
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PMID:Dendritic Cells, the Double Agent in the War Against HIV-1. 3170 24

Toxoplasma gondii, the causative agent of toxoplasmosis and a major opportunistic parasite associated with AIDS, is able to invade host cells of animals and humans. Studies suggested that the ability of host invasion by the tachyzoite, the infectious form of T. gondii, is essential for the pathogenicity to promote its dissemination to other parts of animal hosts. However, the detailed molecular mechanisms for host invasion and dissemination of the parasites are not clear. On the other hand, viruses and bacteria are able to interact with and hijack DC-SIGN (CD209) C-type lectin on antigen presenting cells (APCs), such as dendritic cells and macrophages as the Trojan horses to promote host dissemination. In this study, we showed that invasion of T. gondii into host cells was enhanced by this parasite-CD209 interaction that were inhibited by ligand mimicking-oligosaccharides and the anti-CD209 antibody. Furthermore, covering the exposures of DC-SIGN by these oligosaccharides reduced parasite burden, host spreading and mortality associated with T. gondii infection. These results suggested that interaction of T. gondii to APCs expressing DC-SIGN might promote host dissemination and infection. Can the blockage of this interaction with Mannan and/or anti-CD209 antibody be developed as a prevention or treatment method for T. gondii infection?
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PMID:CD209 C-Type Lectins Promote Host Invasion, Dissemination, and Infection of Toxoplasma gondii. 3239 Oct 4


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