Molecular Insights into HIV-1 Infection

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 3645

Special Issue Editor


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Guest Editor
Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA
Interests: host–pathogen interaction; HIV-1 infection; intra-cellular trafficking of vRNP; biomolecular condensates in virus life cycle
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Special Issue Information

Dear Colleagues,

The FDA’s approval of Lenacapavir, a long-acting HIV-1 prevention drug has marked the year 2025 as a significant milestone in anti-retroviral therapy. Recent advancements and breakthroughs in HIV-1 molecular biology have intensified the race to achieve the development of a complete cure for AIDS. A better understanding of the complex interplay between virus and host cell factors at the molecular level will contribute to developing more effective therapeutic strategies.

This Special Issue, “Molecular Insights into HIV-1 Infection”, seeks manuscripts that investigate the crucial steps of the HIV-1 lifecycle; virus entry into host cell, nuclear trafficking, integration, latency, assembly, egress, and maturation. We additionally encourage the submission of papers that explore the latest technology in this field used to develop novel drug molecules or anti-HIV-1 strategies. Review articles on recent developments in our understanding of HIV-1 biology are also welcome.

We look forward to receiving your submissions, hoping to contribute to the development of innovative strategies against HIV-1.

Dr. Satya Prakash Singh
Guest Editor

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Keywords

  • HIV-1 replication
  • host factors
  • nuclear translocation and integration
  • HIV-1 latency and immune response
  • anti-HIV-1 strategies
  • techniques in HIV research

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Published Papers (3 papers)

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Research

14 pages, 2484 KB  
Article
Mapping the TAR vRNA Interaction with HIV-1 Integrase
by Jian Sun, Rahul Yadav, Tolga Catmakas, Luke Fisher, Nicholas C. Fitzkee and Jacques J. Kessl
Viruses 2026, 18(6), 657; https://doi.org/10.3390/v18060657 (registering DOI) - 9 Jun 2026
Abstract
A series of critical interactions within the viral core between viral RNA (vRNA) and HIV-1 Integrase (IN) has previously been reported. In these studies, contact points between vRNA and IN were identified using RNA-seq and MS-based protein foot-printing approaches. Several IN amino acids [...] Read more.
A series of critical interactions within the viral core between viral RNA (vRNA) and HIV-1 Integrase (IN) has previously been reported. In these studies, contact points between vRNA and IN were identified using RNA-seq and MS-based protein foot-printing approaches. Several IN amino acids located in its C-terminal domain (CTD) were found to be essential for vRNA binding, and their alanine substitution severely impacted the correct morphogenesis of the mature viral core. Here, we have used the TAR element to extend these studies by performing a comprehensive mapping of the interaction by deploying RNA crosslinking and NMR methodologies. Together, these approaches were able to identify additional contact points between the TAR vRNA and IN. Our results reveal several new basic amino acids located in the IN CTD critical for the vRNA-IN interaction, viral replication and correct morphology of the mature viral core. Full article
(This article belongs to the Special Issue Molecular Insights into HIV-1 Infection)
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28 pages, 6939 KB  
Article
Single-Cell Transcriptomic Profile Associated with Sub-Subtype A6 and CRF63-02A6 HIV-1 Strain Infection
by Kirill Elfimov, Anna Khozyainova, Ludmila Gotfrid, Dmitriy Baboshko, Dmitry Kapustin, Polina Achigecheva, Vasiliy Ekushov, Maksim Halikov, Mariya Gashnikova, Tatyana Bauer, Tatyana Tregubchak, Andrey Murzin, Arina Kiryakina, Aleksei Totmenin, Aleksandr Agaphonov and Natalya Gashnikova
Viruses 2026, 18(2), 204; https://doi.org/10.3390/v18020204 - 4 Feb 2026
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Abstract
We present the single-cell transcriptomic analysis of peripheral blood mononuclear cells (PBMC) from individuals during acute HIV-1 infection caused by viral strains circulating in Russia and the Former Soviet Union (FSU) countries. Using 10x Genomics single-cell RNA sequencing (scRNA-seq) on the Illumina NextSeq [...] Read more.
We present the single-cell transcriptomic analysis of peripheral blood mononuclear cells (PBMC) from individuals during acute HIV-1 infection caused by viral strains circulating in Russia and the Former Soviet Union (FSU) countries. Using 10x Genomics single-cell RNA sequencing (scRNA-seq) on the Illumina NextSeq 550 platform, we have analyzed scRNA-seq data from three treatment-naive patients (viral load > 1 × 106 copies/mL, estimated infection duration ≤ 4 weeks) and three healthy donors. Data integration (Seurat, Harmony), automated cell-type annotation (CellTypist), and GeneOntology (GO) enrichment analysis for highly expressed and low-expressed genes revealed a profound reorganization of transcriptional programs across key immune populations, including memory CD4+ and CD8+ T cells, non-classical monocytes and natural killer cells (NK-cells). We observed signatures of hyperactivation of pro-inflammatory pathways (NF-kB, TNF, and type I/II interferon signaling), upregulation of genes associated with cellular migration (CXCR4, CCR7) and metabolic adaptation (oxidative phosphorylation components), alongside a mixed pro- and anti-apoptotic expression profile. Notably, our data pointed to a pronounced dysregulation of the TGF-β and mTOR signaling cascades, disrupted intercellular communication networks—particularly between cytotoxic cells and their regulators—altered expression of genes implicated in disease progression (OLR1, SERPINB2, COPS9) and viral persistence control (NEAT1, NAF1). This work provides an initial single-cell transcriptional atlas characterizing early immune responses to HIV-1 sub-subtypes A6 and CRF63_02A6, the predominant drivers of the HIV epidemic across the FSU region. Full article
(This article belongs to the Special Issue Molecular Insights into HIV-1 Infection)
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17 pages, 1213 KB  
Article
Network Dynamics and Evolutionary Drivers of HIV Drug Resistance in Eastern China, from 2022 to 2024
by Dongqing Cao, Hui Xing, Yi Feng, Jiafeng Zhang, Liangkang Zhou, Zhuojing Jiang, Jinkun Chen and Tingting He
Viruses 2025, 17(11), 1516; https://doi.org/10.3390/v17111516 - 19 Nov 2025
Cited by 1 | Viewed by 1961
Abstract
The increasing prevalence of HIV drug resistance poses a significant challenge. This study aimed to investigate the epidemiological dynamics and molecular characteristics of pretreatment drug resistance (PDR) and acquired drug resistance in Shaoxing, Eastern China. Methods: From 2022 to 2024, 571 newly diagnosed [...] Read more.
The increasing prevalence of HIV drug resistance poses a significant challenge. This study aimed to investigate the epidemiological dynamics and molecular characteristics of pretreatment drug resistance (PDR) and acquired drug resistance in Shaoxing, Eastern China. Methods: From 2022 to 2024, 571 newly diagnosed HIV-infected individuals and 119 individuals with antiretroviral treatment failure were enrolled. Molecular transmission networks and Bayesian analysis were employed to identify key drug-resistant clusters and trace their origins. Results: The overall PDR prevalence was 14.4% (85/571). PDR to non-nucleoside reverse transcriptase inhibitors (NNRTIs) was 9.8% (56/571), significantly higher than to NRTIs (1.1%, 6/571) and PIs (3.7%, 21/571) (χ2 = 50.014, p < 0.001). Molecular network analysis identified large clusters harboring K103N and Q58E resistance mutations within the CRF07_BC subtype. Bayesian analysis estimated their introduction into Shaoxing from Guangdong Province around 2016 and 2017, respectively. Integrated network analysis revealed close linkages between virological failure and newly diagnosed cases, highlighting the role of treatment failure in resistance transmission. Conclusion: Targeted interventions against specific subtypes and transmission clusters, alongside continuous resistance surveillance, are essential to curb the spread of drug-resistant HIV and optimize ART regimens. Full article
(This article belongs to the Special Issue Molecular Insights into HIV-1 Infection)
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