scholarly journals The HIV-1 protein Vpr impairs phagosome maturation by controlling microtubule-dependent trafficking

2015 ◽  
Vol 211 (2) ◽  
pp. 359-372 ◽  
Author(s):  
Audrey Dumas ◽  
Gabrielle Lê-Bury ◽  
Florence Marie-Anaïs ◽  
Floriane Herit ◽  
Julie Mazzolini ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Molecular Basis ◽  
Oxygen Species ◽  
Phagosome Maturation ◽  
Maturation Arrest ◽  
Endosomal Sorting ◽  
Immunodeficiency Virus ◽  
Centripetal Movement ◽  
Hiv 1

Human immunodeficiency virus type 1 (HIV-1) impairs major functions of macrophages but the molecular basis for this defect remains poorly characterized. Here, we show that macrophages infected with HIV-1 were unable to respond efficiently to phagocytic triggers and to clear bacteria. The maturation of phagosomes, defined by the presence of late endocytic markers, hydrolases, and reactive oxygen species, was perturbed in HIV-1–infected macrophages. We showed that maturation arrest occurred at the level of the EHD3/MICAL-L1 endosomal sorting machinery. Unexpectedly, we found that the regulatory viral protein (Vpr) was crucial to perturb phagosome maturation. Our data reveal that Vpr interacted with EB1, p150Glued, and dynein heavy chain and was sufficient to critically alter the microtubule plus end localization of EB1 and p150Glued, hence altering the centripetal movement of phagosomes and their maturation. Thus, we identify Vpr as a modulator of the microtubule-dependent endocytic trafficking in HIV-1–infected macrophages, leading to strong alterations in phagolysosome biogenesis.

scholarly journals Mapping of tetraspanin-enriched microdomains that can function as gateways for HIV-1

2006 ◽  
Vol 173 (5) ◽  
pp. 795-807 ◽  
Author(s):  
Sascha Nydegger ◽  
Sandhya Khurana ◽  
Dimitry N. Krementsov ◽  
Michelangelo Foti ◽  
Markus Thali
Keyword(s):  
Human Immunodeficiency Virus ◽  
Envelope Glycoprotein ◽  
Viral Assembly ◽  
Biological Processes ◽  
Gag Protein ◽  
Endosomal Sorting ◽  
Immunodeficiency Virus ◽  
Virus Expression ◽  
Hiv 1

Specific spatial arrangements of proteins and lipids are central to the coordination of many biological processes. Tetraspanins have been proposed to laterally organize cellular membranes via specific associations with each other and with distinct integrins. Here, we reveal the presence of tetraspanin-enriched microdomains (TEMs) containing the tetraspanins CD9, CD63, CD81, and CD82 at the plasma membrane. Fluorescence and immunoelectron microscopic analyses document that the surface of HeLa cells is covered by several hundred TEMs, each extending over a few hundred nanometers and containing predominantly two or more tetraspanins. Further, we reveal that the human immunodeficiency virus type 1 (HIV-1) Gag protein, which directs viral assembly and release, accumulates at surface TEMs together with the HIV-1 envelope glycoprotein. TSG101 and VPS28, components of the mammalian ESCRT1 (endosomal sorting complex required for transport), which is part of the cellular extravesiculation machinery critical for HIV-1 budding, are also recruited to cell surface TEMs upon virus expression, suggesting that HIV-1 egress can be gated through these newly mapped microdomains.

scholarly journals Molecular Basis for the Relative Substrate Specificity of Human Immunodeficiency Virus Type 1 and Feline Immunodeficiency Virus Proteases

2001 ◽  
Vol 75 (19) ◽  
pp. 9458-9469 ◽  
Author(s):  
Zachary Q. Beck ◽  
Ying-Chuan Lin ◽  
John H. Elder
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amino Acid ◽  
Substrate Specificity ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Feline Immunodeficiency Virus ◽  
Molecular Basis ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT We have used a random hexamer phage library to delineate similarities and differences between the substrate specificities of human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV) proteases (PRs). Peptide sequences were identified that were specifically cleaved by each protease, as well as sequences cleaved equally well by both enzymes. Based on amino acid distinctions within the P3-P3′ region of substrates that appeared to correlate with these cleavage specificities, we prepared a series of synthetic peptides within the framework of a peptide sequence cleaved with essentially the same efficiency by both HIV-1 and FIV PRs, Ac-KSGVF↓VVNGLVK-NH2 (arrow denotes cleavage site). We used the resultant peptide set to assess the influence of specific amino acid substitutions on the cleavage characteristics of the two proteases. The findings show that when Asn is substituted for Val at the P2 position, HIV-1 PR cleaves the substrate at a much greater rate than does FIV PR. Likewise, Glu or Gln substituted for Val at the P2′ position also yields peptides specifically susceptible to HIV-1 PR. In contrast, when Ser is substituted for Val at P1′, FIV PR cleaves the substrate at a much higher rate than does HIV-1 PR. In addition, Asn or Gln at the P1 position, in combination with an appropriate P3 amino acid, Arg, also strongly favors cleavage by FIV PR over HIV PR. Structural analysis identified several protease residues likely to dictate the observed specificity differences. Interestingly, HIV PR Asp30 (Ile-35 in FIV PR), which influences specificity at the S2 and S2′ subsites, and HIV-1 PR Pro-81 and Val-82 (Ile-98 and Gln-99 in FIV PR), which influence specificity at the S1 and S1′ subsites, are residues which are often involved in development of drug resistance in HIV-1 protease. The peptide substrate KSGVF↓VVNGK, cleaved by both PRs, was used as a template for the design of a reduced amide inhibitor, Ac-GSGVFΨ(CH2NH)VVNGL-NH2. This compound inhibited both FIV and HIV-1 PRs with approximately equal efficiency. These findings establish a molecular basis for distinctions in substrate specificity between human and feline lentivirus PRs and offer a framework for development of efficient broad-based inhibitors.

scholarly journals Effects of UVA irradiation, aryl azides, and reactive oxygen species on the orthogonal inactivation of the human immunodeficiency virus (HIV-1)

Virology ◽  
2011 ◽  
Vol 417 (1) ◽  
pp. 221-228 ◽  
Author(s):  
Julie M. Belanger ◽  
Yossef Raviv ◽  
Mathias Viard ◽  
M. Jason de la Cruz ◽  
Kunio Nagashima ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Human Immunodeficiency Virus ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Aryl Azides ◽  
Uva Irradiation ◽  
Immunodeficiency Virus ◽  
Hiv 1

Use of polimerase chain reaction for neonatal diagnosis of human immunodeficiency virus type 1 (HIV-1) perinatal infection

1994 ◽  
Vol 70 (6) ◽  
Author(s):  
Marisa Márcia Mussi-Pinhata ◽  
Maria Célia C. Ferez ◽  
Dimas T. Covas ◽  
Geraldo Duarte ◽  
Márcia L. Isaac ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Perinatal Infection ◽  
Chain Reaction ◽  
Neonatal Diagnosis ◽  
Immunodeficiency Virus ◽  
Hiv 1
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