HIV Accessory Proteins

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "General Virology".

Deadline for manuscript submissions: 28 February 2026 | Viewed by 591

Special Issue Editor


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Guest Editor
Department of Chemistry, University of Florida, Gainesville, FL 32611, USA
Interests: spin-labeling; electron paramagnetic resonance (EPR); molecular motion; conformational sampling; HIV-1 protease; drug-pressure selected mutations; natural polymorphisms
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Special Issue Information

Dear Colleagues,

Viruses, such as HIV and other lentiviruses, encode for proteins termed “accessory proteins” that, while not required for in vitro cell culture, allow for in vivo pathogenesis by allowing lentiviruses to evade innate cellular immune responses. Although decades of research into HIV-1 proteins Nef, Vif, Vpu, Vpr, and Vpx has shed light on how each of these proteins modulates host cellular functions to facilitate viral pathogenicity, research into understanding the mechanisms of interaction of accessory proteins with host systems continues. In addition, insights gleaned from these vast studies find applicability in mechanisms of evasion of host innate immunity against other viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coxsackievirus A16 (CV-A16).

For example, recent studies of Vpu from HIV-1 and ORF3a from SARS-CoV-2 revealed how accessory proteins from these viruses were able to exploit the activation of the stimulator of the interferon genes (STING) pathway, blocking nuclear factor κB (NK-κB) signaling, possibly suggesting the STING pathway as a promising new antiviral strategy (Rui et al, 2025; DOI: 10.1126/scisignal.add6593).

For this Special Issue, we invite the submission of original research and review articles that investigate cellular interactions of accessory proteins, with special emphasis on emergent targets for methods of rational drug design, roles of accessory proteins in liquid–liquid phase separations/molecular condensate, or advances in our understanding of molecular machinery exploited by accessory proteins from HIV. Also welcome are articles that identify novel accessory proteins from other viruses of high importance.

Prof. Dr. Gail E. Fanucci
Guest Editor

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Keywords

  • accessory proteins
  • cellular interactions
  • drug design
  • liquid–liquid phase separations
  • molecular condensate
  • HIV
  • novel accessory proteins from other viruses

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Published Papers (1 paper)

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Research

18 pages, 17264 KB  
Article
Genetic Diversity of Vif and Vpr Accessory Proteins in HIV-1 Group M Clades
by Oxana Galzitskaya, Aleksey Lebedev, Anastasiia Antonova, Ekaterina Mezhenskaya, Anna Glyakina, Evgeniya Deryusheva, Ilya Likhachev and Anna Kuznetsova
Viruses 2026, 18(1), 116; https://doi.org/10.3390/v18010116 - 15 Jan 2026
Viewed by 351
Abstract
Vif and Vpr are HIV-1 accessory proteins that create optimal conditions for viral replication. They are considered as potential targets for the development of therapeutic agents. Natural amino acid substitutions in these proteins have previously been associated with disease progression. The aim of [...] Read more.
Vif and Vpr are HIV-1 accessory proteins that create optimal conditions for viral replication. They are considered as potential targets for the development of therapeutic agents. Natural amino acid substitutions in these proteins have previously been associated with disease progression. The aim of this study was to analyze the genetic diversity of Vif and Vpr in HIV-1 group M clades. A total of 5286 sequences were downloaded and analyzed. For 37 clades in group M, the consensus sequences, amino acid natural variation, and clade-specific amino acid residue substitutions (CSSs) were evaluated. Structural analysis and modeling of consensus sequences were performed for subtypes A1, B, C, and D. The average conservation degree in the HIV-1 group M was 86.4% for Vif and 91.3% for Vpr. In both proteins, the lowest amino acid diversity was observed in sub-subtype A6, and the highest in subtype B. In consensus sequences, the substitutions, which might influence pathogenesis, have been determined: in Vif—22H (11_cpx, 91_cpx) and 136P (A6, 01_AE, 15_01B, 59_01B, 89_BF1, 103_01B, 111_01C, 133_A6B), in Vpr—41N (06_cpx) and 55A (B, 07_BC, 35_01D, 56_cpx, 66_cpx, 66_BF1, 71_BF1, 85_BC, 137_0107). In functional motifs, CSSs associated with changes in the chemical properties of amino acid residues were noted. These findings could be taken into account for the development of therapeutic drugs in the future. No correlation was observed between the subtypes and the spatial organization of the oligomeric structures of Vif and Vpr. Using the structural analysis and modeling, it has been shown for the first time that Vif can interact with APOBEC3G as an oligomer. Full article
(This article belongs to the Special Issue HIV Accessory Proteins)
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