3D Superresolution Studies of the Effect of SERINC5 on Env Glycoprotein Distribution on HIV-1 Particles

ABSTRACT Expression of the human immunodeficiency virus type 1 (HIV-1) Env glycoprotein is stringently regulated in infected cells. The majority of the glycoprotein does not reach the cell surface but rather is retained in the endoplasmic reticulum or a cis-Golgi compartment and subsequently degraded. We here report that Env of various HIV-1 isolates is ubiquitinated at the extracellular domain of gp41 and that Env expression could be increased by lactacystin, a specific proteasome inhibitor, suggesting that the ubiquitin/proteasome system is involved in control of expression and degradation.

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Increased Level and Longevity of Protective Immune Responses Induced by DNA Vaccine Expressing the HIV-1 Env Glycoprotein when Combined withIL-21andIL-15Gene Delivery

The Journal of Immunology ◽

10.4049/jimmunol.177.1.177 ◽

2006 ◽

Vol 177 (1) ◽

pp. 177-191 ◽

Cited By ~ 43

Author(s):

Elizabeth Bolesta ◽

Aleksandra Kowalczyk ◽

Andrzej Wierzbicki ◽

Cheryl Eppolito ◽

Yutaro Kaneko ◽

...

Keyword(s):

Immune Responses ◽

Dna Vaccine ◽

Hiv 1 ◽

Env Glycoprotein

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Antagonism of BST-2/Tetherin Is a Conserved Function of the Env Glycoprotein of Primary HIV-2 Isolates

Journal of Virology ◽

10.1128/jvi.01451-16 ◽

2016 ◽

Vol 90 (24) ◽

pp. 11062-11074 ◽

Cited By ~ 9

Author(s):

Chia-Yen Chen ◽

Masashi Shingai ◽

Sarah Welbourn ◽

Malcolm A. Martin ◽

Pedro Borrego ◽

...

Keyword(s):

Amino Acid ◽

Amino Acid Change ◽

Mixed Population ◽

Single Amino Acid ◽

Amino Acid Difference ◽

Virus Release ◽

Host Restriction ◽

Single Amino Acid Change ◽

Hiv 1 ◽

Env Glycoprotein

ABSTRACTAlthough HIV-2 does not encode avpugene, the ability to antagonize bone marrow stromal antigen 2 (BST-2) is conserved in some HIV-2 isolates, where it is controlled by the Env glycoprotein. We previously reported that a single-amino-acid difference between the laboratory-adapted ROD10 and ROD14 Envs controlled the enhancement of virus release (referred to here as Vpu-like) activity. Here, we investigated how conserved the Vpu-like activity is in primary HIV-2 isolates. We found that half of the 34 tested primary HIV-2 Env isolates obtained from 7 different patients enhanced virus release. Interestingly, most HIV-2 patients harbored a mixed population of viruses containing or lacking Vpu-like activity. Vpu-like activity and Envelope functionality varied significantly among Env isolates; however, there was no direct correlation between these two functions, suggesting they evolved independently. In comparing the Env sequences from one HIV-2 patient, we found that similar to the ROD10/ROD14 Envs, a single-amino-acid change (T568I) in the ectodomain of the TM subunit was sufficient to confer Vpu-like activity to an inactive Env variant. Surprisingly, however, absence of Vpu-like activity was not correlated with absence of BST-2 interaction. Taken together, our data suggest that maintaining the ability to antagonize BST-2 is of functional relevance not only to HIV-1 but also to HIV-2 as well. Our data show that as with Vpu, binding of HIV-2 Env to BST-2 is important but not sufficient for antagonism. Finally, as observed previously, the Vpu-like activity in HIV-2 Env can be controlled by single-residue changes in the TM subunit.IMPORTANCELentiviruses such as HIV-1 and HIV-2 encode accessory proteins whose function is to overcome host restriction mechanisms. Vpu is a well-studied HIV-1 accessory protein that enhances virus release by antagonizing the host restriction factor BST-2. HIV-2 does not encode avpugene. Instead, the HIV-2 Env glycoprotein was found to antagonize BST-2 in some isolates. Here, we cloned multiple Env sequences from 7 HIV-2-infected patients and found that about half were able to antagonize BST-2. Importantly, most HIV-2 patients harbored a mixed population of viruses containing or lacking the ability to antagonize BST-2. In fact, in comparing Env sequences from one patient combined with site-directed mutagenesis, we were able to restore BST-2 antagonism to an inactive Env protein by a single-amino-acid change. Our data suggest that targeting BST-2 by HIV-2 Env is a dynamic process that can be regulated by simple changes in the Env sequence.

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Apoptosis in asymptomatic HIV-1 seropositives immunized with HIV-1 env glycoprotein (gp160): Effects of administration of Zidovudine in vivo and interleukin-2 in vitro

Vaccine ◽

10.1016/s0264-410x(97)00251-x ◽

1998 ◽

Vol 16 (7) ◽

pp. 715-721 ◽

Cited By ~ 2

Author(s):

Marina Pierdominici ◽

Bianca Mollicone ◽

Giovanni Ricci ◽

Alessandra Oliva ◽

Gianpiero D'Offizi ◽

...

Keyword(s):

Interleukin 2 ◽

Hiv 1 ◽

Asymptomatic Hiv ◽

Env Glycoprotein

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Purification, Characterization, and Immunogenicity of a Soluble Trimeric Envelope Protein Containing a Partial Deletion of the V2 Loop Derived from SF162, an R5-Tropic Human Immunodeficiency Virus Type 1 Isolate

Journal of Virology ◽

10.1128/jvi.77.20.11244-11259.2003 ◽

2003 ◽

Vol 77 (20) ◽

pp. 11244-11259 ◽

Cited By ~ 120

Author(s):

Indresh K. Srivastava ◽

Leonidas Stamatatos ◽

Elaine Kan ◽

Michael Vajdy ◽

Ying Lian ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Hydrodynamic Radius ◽

Rhesus Macaques ◽

Partial Deletion ◽

Immunodeficiency Virus ◽

Functional Antibodies ◽

Hiv Envelope ◽

Hiv 1 ◽

Env Glycoprotein

ABSTRACT The envelope (Env) glycoprotein of human immunodeficiency virus type 1 (HIV-1) is the major target of neutralizing antibody responses and is likely to be a critical component of an effective vaccine against AIDS. Although monomeric HIV envelope subunit vaccines (gp120) have induced high-titer antibody responses and neutralizing antibodies against laboratory-adapted HIV-1 strains, they have failed to induce neutralizing antibodies against diverse heterologous primary HIV isolates. Most probably, the reason for this failure is that the antigenic structure(s) of these previously used immunogens does not mimic that of the functional HIV envelope, which is a trimer, and thus these immunogens do not elicit high titers of relevant functional antibodies. We recently reported that an Env glycoprotein immunogen (o-gp140SF162ΔV2) containing a partial deletion in the second variable loop (V2) derived from the R5-tropic HIV-1 isolate SF162, when used in a DNA priming-protein boosting vaccine regimen in rhesus macaques, induced neutralizing antibodies against heterologous subtype B primary isolates as well as protection to the vaccinated animals upon challenge with pathogenic SHIVSF162P4 virus. Here we describe the purification of this protein to homogeneity, its characterization as trimer, and its ability to induce primary isolate-neutralizing responses in rhesus macaques. Optimal mutations in the primary and secondary protease cleavage sites of the env gene were identified that resulted in the stable secretion of a trimeric Env glycoprotein in mammalian cell cultures. We determined the molecular mass and hydrodynamic radius (R h ) using a triple detector analysis (TDA) system. The molecular mass of the oligomer was found to be 324 kDa, close to the expected M w of a HIV envelope trimer protein (330 kDa), and the hydrodynamic radius was 7.27 nm. Negative staining electron microscopy of o-gp140SF162ΔV2 showed that it is a trimer with considerable structural flexibility and supported the data obtained by TDA. The structural integrity of the purified trimeric protein was also confirmed by determinations of its ability to bind the HIV receptor, CD4, and its ability to bind a panel of well-characterized neutralizing monoclonal antibodies. No deleterious effect of V2 loop deletion was observed on the structure and conformation of the protein, and several critical neutralization epitopes were preserved and well exposed on the purified o-gp140SF162ΔV2 protein. In an intranasal priming and intramuscular boosting regimen, this protein induced high titers of functional antibodies, which neutralized the vaccine strain, i.e., SF162. These results highlight a potential role for the trimeric o-gp140SF162ΔV2 Env immunogen in a successful HIV vaccine.

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HIV-1 Env Glycoprotein Phenotype along with Immune Activation Determines CD4 T Cell Loss in HIV Patients

The Journal of Immunology ◽

10.4049/jimmunol.1501588 ◽

2016 ◽

Vol 196 (4) ◽

pp. 1768-1779 ◽

Cited By ~ 17

Author(s):

Anjali Joshi ◽

Melina Sedano ◽

Bethany Beauchamp ◽

Erin B. Punke ◽

Zuber D. Mulla ◽

...

Keyword(s):

T Cell ◽

Immune Activation ◽

Cell Loss ◽

Cd4 T Cell ◽

Hiv Patients ◽

Hiv 1 ◽

Env Glycoprotein

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Induction of cytopathic effects and apoptosis in Spodoptera frugiperda cells by the HIV-1 Env glycoprotein signal peptide

Virus Genes ◽

10.1007/s11262-010-0527-y ◽

2010 ◽

Vol 41 (3) ◽

pp. 341-350 ◽

Cited By ~ 4

Author(s):

Chad James Michalski ◽

Yan Li ◽

C. Yong Kang

Keyword(s):

Signal Peptide ◽

Spodoptera Frugiperda ◽

Cytopathic Effects ◽

Hiv 1 ◽

Env Glycoprotein

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Challenging the Existing Model of the Hexameric HIV-1 Gag Lattice and MA Shell Superstructure: Implications for Viral Entry

Viruses ◽

10.3390/v13081515 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1515

Author(s):

Joy Ramielle L. Santos ◽

Weijie Sun ◽

Tarana A. Mangukia ◽

Eduardo Reyes-Serratos ◽

Marcelo Marcet-Palacios

Keyword(s):

Viral Entry ◽

Specific Antigen ◽

Hexagonal Lattice ◽

Three Dimensional ◽

X Ray Crystallography ◽

Ellipsoidal Shape ◽

Immunodeficiency Virus ◽

Hiv 1 ◽

Env Glycoprotein

Despite type 1 human immunodeficiency virus (HIV-1) being discovered in the early 1980s, significant knowledge gaps remain in our understanding of the superstructure of the HIV-1 matrix (MA) shell. Current viral assembly models assume that the MA shell originates via recruitment of group-specific antigen (Gag) polyproteins into a hexagonal lattice but fails to resolve and explain lattice overlapping that occurs when the membrane is folded into a spherical/ellipsoidal shape. It further fails to address how the shell recruits, interacts with and encompasses the viral spike envelope (Env) glycoproteins. These Env glycoproteins are crucial as they facilitate viral entry by interacting with receptors and coreceptors located on T-cells. In our previous publication, we proposed a six-lune hosohedral structure, snowflake-like model for the MA shell of HIV-1. In this article, we improve upon the six-lune hosohedral structure by incorporating into our algorithm the recruitment of complete Env glycoproteins. We generated the Env glycoprotein assembly using a combination of predetermined Env glycoprotein domains from X-ray crystallography, nuclear magnetic resonance (NMR), cryoelectron tomography, and three-dimensional prediction tools. Our novel MA shell model comprises 1028 MA trimers and 14 Env glycoproteins. Our model demonstrates the movement of Env glycoproteins in the interlunar spaces, with effective clustering at the fusion hub, where multiple Env complexes bind to T-cell receptors during the process of viral entry. Elucidating the HIV-1 MA shell structure and its interaction with the Env glycoproteins is a key step toward understanding the mechanism of HIV-1 entry.

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