Submit to Microorganisms Review for Microorganisms Propose a Special Issue

Journal Menu

Journal Browser

Structural and Functional Biology of Retroviral Entry

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Molecular Microbiology and Immunology".

Deadline for manuscript submissions: closed (31 May 2021) | Viewed by 21395

Share This Special Issue

Special Issue Editor

Dr. Andrés Finzi

E-Mail Website
Guest Editor

Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montreal, QC H3C 3T5, Canada
Interests: HIV; Env conformation; neutralizing and non-neutralizing Abs; ADCC; small molecule entry inhibitors; HIV accessory proteins; CD4; neutralization
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

HIV and SIV envelope glycoproteins (Env) are the only virus-specific proteins on the surface of viral particles and infected cells. They are the target of host neutralizing and non-neutralizing antibodies. A major hurdle to target Env is their variability and conformational flexibility. Recent advances in Env conformational dynamics together with new structural information are unveiling unsuspected new barriers to develop effective interventions.

In this Special Issue, we welcome research papers and review articles related to all aspects of HIV and SIV entry that will help provide a comprehensive view of this rapidly evolving field. Topics may include (but are not limited to) viral entry, Env conformation, immunogen design, neutralizing and non-neutralizing antibodies, Fc-mediated effector functions, and additional immune correlates of protection.

Dr. Andrés Finzi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

HIV
SIV
SHIV
entry
fusion
vaccine
immunogen
neutralizing antibodies
non-neutralizing antibodies
ADCC
immune correlates of protection

Published Papers (5 papers)

Download All Papers

Research

Jump to: Review

19 pages, 2809 KiB

Open AccessArticle

Peptide Triazole Thiol Irreversibly Inactivates Metastable HIV-1 Env by Accessing Conformational Triggers Intrinsic to Virus–Cell Entry

by Charles Gotuaco Ang, Erik Carter, Ann Haftl, Shiyu Zhang, Adel A. Rashad, Michele Kutzler, Cameron F. Abrams and Irwin M. Chaiken

Microorganisms 2021, 9(6), 1286; https://doi.org/10.3390/microorganisms9061286 - 12 Jun 2021

Cited by 3 | Viewed by 2154

Abstract

KR13, a peptide triazole thiol previously established to inhibit HIV-1 infection and cause virus lysis, was evaluated by flow cytometry against JRFL Env-presenting cells to characterize induced Env and membrane transformations leading to irreversible inactivation. Transiently transfected HEK293T cells were preloaded with calcein dye, treated with KR13 or its thiol-blocked analogue KR13b, fixed, and stained for gp120 (35O22), MPER (10E8), 6-helix-bundle (NC-1), immunodominant loop (50-69), and fusion peptide (VRC34.01). KR13 induced dose-dependent transformations of Env and membrane characterized by transient poration, MPER exposure, and 6-helix-bundle formation (analogous to native fusion events), but also reduced immunodominant loop and fusion peptide exposure. Using a fusion peptide mutant (V504E), we found that KR13 transformation does not require functional fusion peptide for poration. In contrast, simultaneous treatment with fusion inhibitor T20 alongside KR13 prevented membrane poration and MPER exposure, showing that these events require 6-helix-bundle formation. Based on these results, we formulated a model for PTT-induced Env transformation portraying how, in the absence of CD4/co-receptor signaling, PTT may provide alternate means of perturbing the metastable Env-membrane complex, and inducing fusion-like transformation. In turn, the results show that such transformations are intrinsic to Env and can be diverted for irreversible inactivation of the protein complex. Full article

(This article belongs to the Special Issue Structural and Functional Biology of Retroviral Entry)

► Show Figures

Figure 1

17 pages, 12855 KiB

Open AccessArticle

Effects of gp120 Inner Domain (ID2) Immunogen Doses on Elicitation of Anti-HIV-1 Functional Fc-Effector Response to C1/C2 (Cluster A) Epitopes in Mice

by Rebekah Sherburn, William D. Tolbert, Suneetha Gottumukkala, Guillaume Beaudoin-Bussières, Andrés Finzi and Marzena Pazgier

Microorganisms 2020, 8(10), 1490; https://doi.org/10.3390/microorganisms8101490 - 28 Sep 2020

Cited by 1 | Viewed by 1722

Abstract

Fc-mediated effector functions of antibodies, including antibody-dependent cytotoxicity (ADCC), have been shown to contribute to vaccine-induced protection from HIV-1 infection, especially those directed against non-neutralizing, CD4 inducible (CD4i) epitopes within the gp120 constant 1 and 2 regions (C1/C2 or Cluster A epitopes). However, recent passive immunization studies have not been able to definitively confirm roles for these antibodies in HIV-1 prevention mostly due to the complications of cross-species Fc–FcR interactions and suboptimal dosing strategies. Here, we use our stabilized gp120 Inner domain (ID2) immunogen that displays the Cluster A epitopes within a minimal structural unit of HIV-1 Env to investigate an immunization protocol that induces a fine-tuned antibody repertoire capable of an effective Fc-effector response. This includes the generation of isotypes and the enhanced antibody specificity known to be vital for maximal Fc-effector activities, while minimizing the induction of isotypes know to be detrimental for these functions. Although our studies were done in in BALB/c mice we conclude that when optimally titrated for the species of interest, ID2 with GLA-SE adjuvant will elicit high titers of antibodies targeting the Cluster A region with potent Fc-mediated effector functions, making it a valuable immunogen candidate for testing an exclusive role of non-neutralizing antibody response in HIV-1 protection in vaccine settings. Full article

(This article belongs to the Special Issue Structural and Functional Biology of Retroviral Entry)

► Show Figures

Figure 1

12 pages, 1773 KiB

Open AccessArticle

Elicitation of Cluster A and Co-Receptor Binding Site Antibodies Are Required to Eliminate HIV-1 Infected Cells

by Guillaume Beaudoin-Bussières, Jérémie Prévost, Gabrielle Gendron-Lepage, Bruno Melillo, Junhua Chen, Amos B. Smith III, Marzena Pazgier and Andrés Finzi

Microorganisms 2020, 8(5), 710; https://doi.org/10.3390/microorganisms8050710 - 11 May 2020

Cited by 6 | Viewed by 2683

Abstract

HIV-1-infected individuals raise a polyclonal antibody response targeting multiple envelope glycoprotein (Env) epitopes. Interestingly, two classes of non-neutralizing CD4-induced (CD4i) antibodies, present in the majority of HIV-1-infected individuals have been described to mediate antibody-dependent cellular cytotoxicity (ADCC) in the presence of small CD4 mimetic compounds (CD4mc). These antibodies recognize the coreceptor binding site (CoRBS) and the constant region one and two (C1C2 or inner domain cluster A) of the gp120. In combination with CD4mc they have been shown to stabilize an antibody-vulnerable Env conformation, known as State 2A. Here we evaluated the importance of these two families of Abs in ADCC responses by immunizing guinea pigs with gp120 immunogens that have been modified to elicit or not these types of antibodies. Underlying the importance of anti-CoRBS and anti-cluster A Abs in stabilizing State 2A, ADCC responses were only observed in the presence of these two types of CD4i antibodies. Altogether, our results suggest that these two families of CD4i antibodies must be taken into account when considering future strategies relying on the use of CD4mc to eliminate HIV-1-infected cells in vivo. Full article

(This article belongs to the Special Issue Structural and Functional Biology of Retroviral Entry)

► Show Figures

Figure 1

Review

Jump to: Research

61 pages, 8662 KiB

Open AccessReview

SARS-CoV-2 Portrayed against HIV: Contrary Viral Strategies in Similar Disguise

by Ralf Duerr, Keaton M. Crosse, Ana M. Valero-Jimenez and Meike Dittmann

Microorganisms 2021, 9(7), 1389; https://doi.org/10.3390/microorganisms9071389 - 27 Jun 2021

Cited by 6 | Viewed by 8534

Abstract

SARS-CoV-2 and HIV are zoonotic viruses that rapidly reached pandemic scale, causing global losses and fear. The COVID-19 and AIDS pandemics ignited massive efforts worldwide to develop antiviral strategies and characterize viral architectures, biological and immunological properties, and clinical outcomes. Although both viruses have a comparable appearance as enveloped viruses with positive-stranded RNA and envelope spikes mediating cellular entry, the entry process, downstream biological and immunological pathways, clinical outcomes, and disease courses are strikingly different. This review provides a systemic comparison of both viruses’ structural and functional characteristics, delineating their distinct strategies for efficient spread. Full article

(This article belongs to the Special Issue Structural and Functional Biology of Retroviral Entry)

► Show Figures

Figure 1

32 pages, 1888 KiB

Open AccessReview

HIV-1 Entry and Prospects for Protecting against Infection

by Jean-François Bruxelle, Nino Trattnig, Marianne W. Mureithi, Elise Landais and Ralph Pantophlet

Microorganisms 2021, 9(2), 228; https://doi.org/10.3390/microorganisms9020228 - 22 Jan 2021

Cited by 8 | Viewed by 5694

Abstract

Human Immunodeficiency Virus type-1 (HIV-1) establishes a latent viral reservoir soon after infection, which poses a major challenge for drug treatment and curative strategies. Many efforts are therefore focused on blocking infection. To this end, both viral and host factors relevant to the onset of infection need to be considered. Given that HIV-1 is most often transmitted mucosally, strategies designed to protect against infection need to be effective at mucosal portals of entry. These strategies need to contend also with cell-free and cell-associated transmitted/founder (T/F) virus forms; both can initiate and establish infection. This review will discuss how insight from the current model of HIV-1 mucosal transmission and cell entry has highlighted challenges in developing effective strategies to prevent infection. First, we examine key viral and host factors that play a role in transmission and infection. We then discuss preventive strategies based on antibody-mediated protection, with emphasis on targeting T/F viruses and mucosal immunity. Lastly, we review treatment strategies targeting viral entry, with focus on the most clinically advanced entry inhibitors. Full article

(This article belongs to the Special Issue Structural and Functional Biology of Retroviral Entry)

► Show Figures