A5056321337- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- interferon and immune responses
- Hepatitis C virus research
- T-cell and B-cell Immunology
- HIV/AIDS Research and Interventions
- Protein Structure and Dynamics
- Glycosylation and Glycoproteins Research
- Herpesvirus Infections and Treatments
- Protein purification and stability
- Cytomegalovirus and herpesvirus research
- Enzyme Structure and Function
- Viral Infections and Vectors
- Antimicrobial Peptides and Activities
- Viral Infections and Immunology Research
- RNA and protein synthesis mechanisms
- Chemokine receptors and signaling
- Immunotherapy and Immune Responses
- Ethics in Clinical Research
- Ubiquitin and proteasome pathways
- Hepatitis B Virus Studies
- Mosquito-borne diseases and control
- Lipid Membrane Structure and Behavior
Universidad Complutense de Madrid
1999-2023
Centro Nacional de Biotecnología
2019-2023
Universidad Autónoma de Madrid
2014-2019
Centre Hospitalier de l’Université de Montréal
2016-2018
Dana-Farber Cancer Institute
2007-2017
Harvard University
2006-2017
Centro de Biología Molecular Severo Ochoa
2013-2016
Consejo Superior de Investigaciones Científicas
2014-2016
University of California, San Diego
2012
University of Baltimore
2012
Human immunodeficiency virus (HIV-1) enters cells following sequential activation of the high-potential-energy viral envelope glycoprotein trimer by target cell CD4 and coreceptor. HIV-1 variants differ in their requirements for CD4; viruses that can infect coreceptor-expressing lack have been generated laboratory. These CD4-independent are sensitive to neutralization multiple antibodies recognize different epitopes. The mechanisms underlying independence, global sensitivity association...
Human immunodeficiency virus type 1 (HIV-1) has evolved a sophisticated strategy to conceal conserved epitopes of its envelope glycoproteins (Env) recognized by antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies. These antibodies, which are present in the sera most HIV-1-infected individuals, preferentially recognize Env CD4-bound conformation. Accordingly, recent studies showed that small CD4-mimetics (CD4mc) able "push" into this conformation sensitize cells ADCC mediated...
ABSTRACT Human immunodeficiency virus (HIV-1) entry into cells is mediated by a trimeric complex consisting of noncovalently associated gp120 (exterior) and gp41 (transmembrane) envelope glycoproteins. The binding to receptors on the target cell alters gp120-gp41 relationship activates membrane-fusing capacity gp41. Interaction with primary receptor, CD4, results in exposure third variable (V3) loop, which contributes CCR5 or CXCR4 chemokine receptors. We show here that insertions V3 stem...
ABSTRACT Interactions between the gp120 and gp41 subunits of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer maintain metastable unliganded form viral spike. Binding to receptor, CD4, changes Env conformation promote interaction with second CCR5 or CXCR4. CD4 binding also induces transformation into prehairpin intermediate, in which heptad repeat (HR1) coiled coil is assembled at axis. In nature, HIV-1 Envs must balance requirements noncovalent association...
HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibody-dependent cellular-mediated cytotoxicity (ADCC). HIV-1 has evolved sophisticated mechanisms to avoid exposure of Env ADCC epitopes downregulating CD4 and limiting overall amount cell surface. In HIV-1, substitution large residues such as histidine or tryptophan for serine 375 (S375H/W) gp120 Phe 43 cavity, where contacts gp120, results...
ABSTRACT The trimeric envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) mediates entry into host cells. CD4 engagement with the gp120 exterior subunit represents first step during HIV-1 entry. CD4-induced conformational changes in inner domain involve three potentially flexible topological layers (layers 1, 2, and 3). Structural rearrangements between layer 2 have been shown to facilitate transition trimer from unliganded CD4-bound state stabilize gp120-CD4...
ABSTRACT The mature envelope glycoprotein (Env) spike on the surfaces of human immunodeficiency virus type 1 (HIV-1)-infected cells and virions is derived from proteolytic cleavage a trimeric gp160 precursor. In these studies, we compared conformations cleaved uncleaved membrane Envs with truncated cytoplasmic tails to those stabilized soluble gp140 SOSIP.664 Env trimers. Deletion gp41 tail did not significantly affect sensitivity viruses HIV-1 AD8 inhibition by antibodies or CD4-mimetic...
Foamy virus evolution closely parallels that of the host species, indicating virus-host coadaptation. We studied simian foamy viruses (SFVs) from common marmosets, spider monkeys, and squirrel New World monkey (NWM) species share geographic ranges. The TRIM5alpha protein each these NWM inhibited replication at least one SFVs associated with other two but did not affect its own SFV. Thus, has potentially shaped in hosts. Conversely, may have influenced TRIM5 variants primates.
Metastable conformations of the gp120 and gp41 envelope glycoproteins human immunodeficiency virus type 1 (HIV-1) simian (SIV) must be maintained in unliganded state glycoprotein trimer. Binding to primary receptor, CD4, triggers transition an open conformation trimer, promoting interaction with CCR5 chemokine receptor ultimately leading gp41-mediated virus-cell membrane fusion entry. Topological layers inner domain contribute gp120-trimer association CD4 binding. Here we describe...
HIV-1 entry involves the viral envelope glycoproteins (Env gps) and receptors on target cell. Receptor binding channels intrinsic high potential energy of Env into force required to fuse membranes virus For some strains, prolonged incubation ice decreases results in functional inactivation. By characterizing chimeras between two primary clade C strains that differ sensitivities cold, soluble CD4, neutralizing antibodies, we found these properties were largely determined by discrete elements...
ABSTRACT The tripartite motif protein TRIM5α restricts particular retrovirus infections by binding to the incoming capsid and inhibiting early stage of virus infection. RING domain exhibits E3 ubiquitin ligase activity assists higher-order association dimers, which promotes binding. We characterized a panel mutants rhesus monkey (TRIM5α rh ) protein. function that significantly contributed retroviral restriction depended upon restricted virus. contributes potency HIV-1 restriction....
ABSTRACT Previous studies have shown that highly conserved residues in the inner domain of gp120 are required for HIV-1 envelope glycoprotein (Env) transitions to CD4-bound conformation (A. Finzi, S. H. Xiang, B. Pacheco, L. Wang, J. Haight, et al., Mol Cell 37: 656–667, 2010, http://dx.doi.org/10.1016/j.molcel.2010.02.012 ; A. Desormeaux, M. Coutu, Medjahed, Herschhorn, J Virol 87: 2549–2562, 2013, http://dx.doi.org/10.1128/JVI.03104-12 ). Moreover, W69, a residue located at interface...
ABSTRACT Human immunodeficiency virus type 1 (HIV-1) infection encounters an early block in the cells of New World monkeys because CD4 receptor does not efficiently support HIV-1 entry. We adapted HIV-1(NL4-3) and HIV-1(KB9), two variants with different envelope glycoproteins, to replicate expressing CXCR4 proteins common marmoset, a monkey. The adaptation involves three gp120 changes that result specific increase affinity for marmoset glycoprotein. already high HIV-1(KB9) glycoproteins did...
Abstract Gp120 is a critical component of the envelope HIV-1. Its role in viral entry well described. In view its position on envelope, gp120 part retrovirus that immune cells encounter first and has potential to influence antiretroviral responses. We propose high levels are present tissues may contribute failure system fully control ultimately clear virus. Herein, we show for time lymphoid from acutely HIV-1/SIV (SHIV)-KB9-infected macaques contain deposits at concentrations enough induce...