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1. “Pseudomonas Phage ZCPS1 Endolysin as a Potential Therapeutic Agent”
by Fatma Abdelrahman, Rutuja Gangakhedkar, Gokul Nair, Gamal El-Didamony, Ahmed Askora, Vikas Jain and Ayman El-Shibiny
Viruses 2023, 15(2), 520; https://doi.org/10.3390/v15020520
Available online: https://www.mdpi.com/1999-4915/15/2/520

2. “Characterization and Anti-Biofilm Activity of Lytic Enterococcus Phage vB_Efs8_KEN04 against Clinical Isolates of Multidrug-Resistant Enterococcus faecalis in Kenya”
by Oumarou Soro, Collins Kigen, Andrew Nyerere, Moses Gachoya, Martin Georges, Erick Odoyo and Lillian Musila
Viruses 2024, 16(8), 1275; https://doi.org/10.3390/v16081275
Available online: https://www.mdpi.com/1999-4915/16/8/1275

3. “Short-Term Outcomes of Phage-Antibiotic Combination Treatment in Adult Patients with Periprosthetic Hip Joint Infection”
by Eugeny Fedorov, Alexander Samokhin, Yulia Kozlova, Svetlana Kretien, Taalai Sheraliev, Vera Morozova, Nina Tikunova, Alexey Kiselev and Vitaliy Pavlov
Viruses 2023, 15(2), 499; https://doi.org/10.3390/v15020499
Available online: https://www.mdpi.com/1999-4915/15/2/499

4. “Design of Phage-Cocktail–Containing Hydrogel for the Treatment of Pseudomonas aeruginosa–Infected Wounds”
by Fatemeh Shafigh Kheljan, Farzam Sheikhzadeh Hesari, Mohammad Sadegh Aminifazl, Mikael Skurnik, Sophia Goladze and Gholamreza Zarrini
Viruses 2023, 15(3), 803; https://doi.org/10.3390/v15030803
Available online: https://www.mdpi.com/1999-4915/15/3/803

5. “Successful Bacteriophage-Antibiotic Combination Therapy against Multidrug-Resistant Pseudomonas aeruginosa Left Ventricular Assist Device Driveline Infection”
by Karlis Racenis, Janis Lacis, Dace Rezevska, Laima Mukane, Aija Vilde, Ints Putnins, Sarah Djebara, Maya Merabishvili, Jean-Paul Pirnay, Marika Kalnina et al.
Viruses 2023, 15(5), 1210; https://doi.org/10.3390/v15051210
Available online: https://www.mdpi.com/1999-4915/15/5/1210

6. “Phage and Antibiotic Combinations Reduce Staphylococcus aureus in Static and Dynamic Biofilms Grown on an Implant Material”
by Hyonoo Joo, Sijia M. Wu, Isha Soni, Caroline Wang-Crocker, Tyson Matern, James Peter Beck and Catherine Loc-Carrillo
Viruses 2023, 15(2), 460; https://doi.org/10.3390/v15020460  
Available online: https://www.mdpi.com/1999-4915/15/2/460

7. “The Lytic Activity of Bacteriophage ZCSE9 against Salmonella enterica and Its Synergistic Effects with Kanamycin”
by Abdallah S. Abdelsattar, Mohamed Atef Eita, Zainab K. Hammouda, Shrouk Mohamed Gouda, Toka A. Hakim, Aghapy Yermans Yakoup, Anan Safwat and Ayman El-Shibiny
Viruses 2023, 15(4), 912; https://doi.org/10.3390/v15040912
Available online: https://www.mdpi.com/1999-4915/15/4/912

8. “Biological Properties of 12 Newly Isolated Acinetobacter baumannii-Specific Bacteriophages”
by Natalia Bagińska, Marek Adam Harhala, Martyna Cieślik, Filip Orwat, Beata Weber-Dąbrowska, Krystyna Dąbrowska, Andrzej Górski and Ewa Jończyk-Matysiak
Viruses 2023, 15(1), 231; https://doi.org/10.3390/v15010231
Available online: https://www.mdpi.com/1999-4915/15/1/231

9. “Effective Treatment of Staphylococcus aureus Intramammary Infection in a Murine Model Using the Bacteriophage Cocktail StaphLyse™”
by Eric Brouillette, Guillaume Millette, Suzanne Chamberland, Jean-Pierre Roy, Céline Ster, Tadele Kiros, Stephanie Hickey, Lauren Hittle, Joelle Woolston and François Malouin
Viruses 2023, 15(4), 887; https://doi.org/10.3390/v15040887
Available online: https://www.mdpi.com/1999-4915/15/4/887

10. “Combinations of Bacteriophage Are Efficacious against Multidrug-Resistant Pseudomonas aeruginosa and Enhance Sensitivity to Carbapenem Antibiotics”
by Christopher J. Kovacs, Erika M. Rapp, William R. Rankin, Sophia M. McKenzie, Brianna K. Brasko, Katherine E. Hebert, Beth A. Bachert, Andrew R. Kick, F. John Burpo and Jason C. Barnhill
Viruses 2024, 16(7), 1000; https://doi.org/10.3390/v16071000
Available online: https://www.mdpi.com/1999-4915/16/7/1000

1. “Development of a Ferritin Protein Nanoparticle Vaccine with PRRSV GP5 Protein”
by Xinjian Chang, Jun Ma, Yanrong Zhou, Shaobo Xiao, Xun Xiao and Liurong Fang
Viruses 2024, 16(6), 991; https://doi.org/10.3390/v16060991
Available online: https://www.mdpi.com/1999-4915/16/6/991

2. “Genetic Characterization and Pathogenicity of a Recombinant Porcine Reproductive and Respiratory Syndrome Virus Strain in China”
by Yan Ouyang, Yingbing Du, Hejin Zhang, Jiahui Guo, Zheng Sun, Xiuxin Luo, Xiaowei Mei, Shaobo Xiao, Liurong Fang and Yanrong Zhou
Viruses 2024, 16(6), 993; https://doi.org/10.3390/v16060993
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3. “The Full-Genome Analysis and Generation of an Infectious cDNA Clone of a Genotype 6 Hepatitis E Virus Variant Obtained from a Japanese Wild Boar: In Vitro Cultivation in Human Cell Lines”
by Putu Prathiwi Primadharsini, Masaharu Takahashi, Tsutomu Nishizawa, Yukihiro Sato, Shigeo Nagashima, Kazumoto Murata and Hiroaki Okamoto
Viruses 2024, 16(6), 842; https://doi.org/10.3390/v16060842
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4. “Prevalence, Time of Infection, and Diversity of Porcine Reproductive and Respiratory Syndrome Virus in China”
by Chaosi Li, Aihua Fan, Zhicheng Liu, Gang Wang, Lei Zhou, Hongliang Zhang, Lv Huang, Jianfeng Zhang, Zhendong Zhang and Yan Zhang
Viruses 2024, 16(5), 774; https://doi.org/10.3390/v16050774
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5. “Molecular Survey on Porcine Parvoviruses (PPV1-7) and Their Association with Major Pathogens in Reproductive Failure Outbreaks in Northern Italy”
by Giulia Faustini, Claudia Maria Tucciarone, Giovanni Franzo, Anna Donneschi, Maria Beatrice Boniotti, Giovanni Loris Alborali and Michele Drigo
Viruses 2024, 16(1), 157; https://doi.org/10.3390/v16010157  
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6. “Short Treatment of 42 Days with Oral GS-441524 Results in Equal Efficacy as the Recommended 84-Day Treatment in Cats Suffering from Feline Infectious Peritonitis with Effusion—A Prospective Randomized Controlled Study”
by Anna-M. Zuzzi-Krebitz, Katharina Buchta, Michèle Bergmann, Daniela Krentz, Katharina Zwicklbauer, Roswitha Dorsch, Gerhard Wess, Andrea Fischer, Kaspar Matiasek, Anne Hönl et al.
Viruses 2024, 16(7), 1144; https://doi.org/10.3390/v16071144
Available online: https://www.mdpi.com/1999-4915/16/7/1144

7. “Recent Molecular Characterization of Porcine Rotaviruses Detected in China and Their Phylogenetic Relationships with Human Rotaviruses”
by Mengli Qiao, Meizhen Li, Yang Li, Zewei Wang, Zhiqiang Hu, Jie Qing, Jiapei Huang, Junping Jiang, Yaqin Jiang, Jinyong Zhang, Chunliu Gao, Chen Yang, Xiaowen Li and Bin Zhou
Viruses 2024, 16(3), 453; https://doi.org/10.3390/v16030453
Available online: https://www.mdpi.com/1999-4915/16/3/453

8. “Spatial Transmission Characteristics of the Bluetongue Virus Serotype 3 Epidemic in The Netherlands, 2023”
by Gert-Jan Bounder, Thomas J. Hagenaars, Melle Holwerda, Marcel A. H. Spierenburg, Piet A. van Rijn, Arco N. van der Spek and Armin R. W. Elbers
Viruses 2024, 16(4), 625; https://doi.org/10.3390/v16040625
Available online: https://www.mdpi.com/1999-4915/16/4/625

9. “Serologic, Virologic and Pathologic Features of Cats with Naturally Occurring Feline Infectious Peritonitis Enrolled in Antiviral Clinical Trials”
by Brian G. Murphy, Diego Castillo, N E Neely, Amir Kol, Terza Brostoff, Chris K. Grant and Krystle L. Reagan
Viruses 2024, 16(3), 462; https://doi.org/10.3390/v16030462
Available online: https://www.mdpi.com/1999-4915/16/3/462

10. “Geographical Expansion of Avian Metapneumovirus Subtype B: First Detection and Molecular Characterization of Avian Metapneumovirus Subtype B in US Poultry”
by Muhammad Luqman, Naveen Duhan, Gun Temeeyasen, Mohamed Selim, Sumit Jangra and Sunil Kumar Mor
Viruses 2024, 16(4), 508; https://doi.org/10.3390/v16040508
Available online: https://www.mdpi.com/1999-4915/16/4/508

“Picornavirus Evolution: Genomes Encoding Multiple 2ANPGP Sequences—Biomedical and Biotechnological Utility”
by Garry A. Luke, Lauren S. Ross, Yi-Ting Lo, Hsing-Chieh Wu and Martin D. Ryan
Viruses 2024, 16(10), 1587; https://doi.org/10.3390/v16101587
Available online: https://www.mdpi.com/1999-4915/16/10/1587

This accompaniment to the publication proper tells the story behind the paper, detailing the highs and lows along the way.

First identified in foot-and-mouth disease virus (FMDV), the 2A oligopeptide sequence allows multiple discrete proteins to be synthesized from a single strand of virus RNA, which also functions as a messenger RNA (mRNA). The short 2A peptide, 18 amino acids (aa) in length, comprises two parts, an N-terminal region (without high sequence conservation) and a conserved motif comprising the seven C-terminal residues of 2A and the N-terminal proline of the downstream protein 2B (-D[V/I]ExNPG^↓P, underlined proline comprises the N-terminal residue of 2B). Briefly, the 2A region of the polyprotein manipulates the ribosome to “skip” the synthesis of the glycyl-prolyl peptide bond at its own carboxyl terminus leading to the release of the nascent protein followed by translation of the remaining downstream sequence ⁽¹⁾.

Probing databases with this “signature” motif, 2A^NPGP sequences have been reported in several viral genomes within different genera of the Picornaviridae, other positive strand viruses such as the Dicistroviridae and Iflaviridae^(2-3), double-strand RNA viruses belonging to the Totiviridae/Reoviridae  ⁽⁴⁾ families, and in a tentatively assigned negative-sense single-stranded RNA virus of the Bunyaviridae family ⁽³⁾. From bioinformatics analysis, 2A-like cellular sequences have also been identified in the open reading frames (ORFs) of CATERPILLER proteins that are involved in innate immunity⁽⁵⁾, non-LTR retrotransposons (non-LTRs) within the genome of trypanosomes⁽⁶⁾, and a wide range of primitive marine organisms, including sponges, sea slugs, purple sea urchins, acorn worms and amphioxi ⁽⁷⁾. Linking proteins with 2A or 2A-like peptide sequences results in cellular expression of multiple, discrete proteins derived from a single ORF. Of the many 2A peptides identified to date, four viral 2As have been widely used in biotechnology and biomedicine: FMDV (F2A; -QLLNFDLLKLAGDVESNPGP-), equine rhinitis A virus (E2A; -QCTNYALLKLAGDVESNPGP-), porcine teschovirus-1 (P2A; -ATNFSLLKQAGDVEENPGP-), and Thosea asigna virus (T2A; -EGRGSLLTCGDVESNPGP-) ⁽⁸⁾. These sequences are now being used to treat cancer, to produce antibodies and antigens that can be used in vaccine production, genome (DNA and RNA) editing in cell/gene therapies, and engineering multi-gene biosynthetic pathways amongst a host of other biomedical/biotechnological applications (https://www.st-andrews.ac.uk/ryanlab/Index.html). The positive strand RNA viruses typically possess one 2A/2A-like sequence, but some viruses have two, three, or more motifs. The primary aims of our recent paper were to identify genomes containing more than a single 2A^NPGP sequence in the family Picornaviridae, describe their occurrence in different viral genera, and determine their cleavage activity vis à vis potential biotechnology applications.

As a first step, in silico searches of picornavirus proteinase/polymerase and classical 2A^NPGP sequences (-D(V/I)ExNPGP-; -G(V/I)ExNPGP-; “x” is any amino acid which is not conserved) were made by screening the sequences currently available in the NCBI’s (National Centre for Biotechnology Information) growing database. Alignment of 3CD amino acid sequences revealed this family evolved into five “supergroups” (SG1-5; Caphthovirinae, Kodimesavirinae, Ensavirinae, Paavivirinae, and Heptrevirinae) with 2A^NPGP sequences found only within supergroups 1 and 4. Interestingly, the nature of the 2A region of the picornavirus polyprotein was highly correlated with this division of the family ⁽⁹⁾. In the case of the Caphthovirinae (SG1), most if not all viruses encoded a single copy of 2A^NPGP whilst members of the Paavivirinae (SG4) exhibited the highest variability in their 2A region with many viruses encoding multiple 2A^NPGP sequences (e.g., aali-, avisi-, grusopi-, kunsagi-, limnipi-, parecho-, and potamipiviruses) (Figure 1). For instance, the Duck Picornavirus GL/12 (aalivirus A1) has six 2A proteins (Figure 2, Panel A) — the first four all have C-terminal region (~25aa) similarity with the aphthovirus-like 2A^NPGP sequences whilst 2A5 and 2A6 closely resemble avihepatovirus 2A2 and 2A3, respectively ⁽¹⁰⁾.

Figure 1

Figure 2

These multiple 2A^NPGP sequences were then tested for translational recoding activity using our pSTA1 dual reporter system [GFP-2A-GUS] ⁽²⁾. Plasmids containing 2A-like sequences were used to programme a Wheat Germ Extract coupled transcription/translation system and proteins resolved by SDS-PAGE separation (Figure 2, Panel B). Constructs were evaluated for recoding activity relative to the positive FMDV 2A control by visual inspection: [GFP2A] + GUS for high activity, [GFP-2A-GUS] + GUS + [GFP2A] for high/moderate activity, and [GFP-2A-GUS] for no activity. Careful analysis of the translational profiles was both surprising and bewildering. Several sequences displayed higher activity than FMDV 2A and could prove useful for future biotechnological applications: aalivirus A1/B1 2A1-2A4; Grusopivirus A1/C 2A1-2A3; Limnipivirus A1 2A1, B1 2A2, C1 2A1, D1 2A1-3; and Mosavirus B1 2A1 and 2A2 (Table 1). In a number of cases, however, only [GFP2A] could be detected: kunsagivirus C1 2A1, limnipivirus A1 2A2, limnipivirus B1 2A1, potamipivirus B1 2A2, Wuhan carp picornavirus (WCP) 2A1/2A2/2A3, and Wenzhou picorna-like virus 48 (WP-LV48) 2A1/2A2 and 2A3. In terms of our current model of ribosome skipping and virus functionality, an enigma wrapped in a conundrum. In our study, we draw a parallel with no-go decay (NGD), a eukaryote translation-coupled mRNA quality control system ⁽¹¹⁾. NGD, one of at least three mRNA surveillance pathways that include nonsense-mediated decay (NMD) and non-stop decay (NSD), is triggered by the presence of mRNA secondary structures leading to ribosome stalling. Persistent stalling sets in motion a cascade of events that aim to inhibit translation re-initiation on the defective mRNA and simultaneously remove faulty mRNAs and recycle the ribosomes in a process mediated by the Pelota/Hbs1/ABCE1 complex ⁽¹²⁾. Consistent with our observations, this would produce [GFP2A] alone, although the NGD pathway implies degradation of the virus RNA, which is perhaps the most important question yet to be addressed.

Table 1. 2A/2A-like sequences used for protein co-expression

References

1. Donnelly, M.L.L.; Luke, G.A.; Mehotra, A.; Li, X.; Hughes, L.E.; Gani, D.; Ryan, M.D. Analysis of the aphthovirus 2A/2B polyprotein “cleavage” mechanism indicates not a proteolytic reaction, but a novel translational effect: A putative ribosomal “skip”. Gen. Virol. 2001, 82, 1013–1025. https://doi.org/10.1099/0022-1317-82-5-1013. PMID: 11297676.
2. Luke, G.A.; de Felipe, P.; Lukashev, A.; Kallioinen, S.E.; Bruno, E.A.; Ryan, M.D. The occurrence, function, and evolutionary origins of “2A-like” sequences in virus genomes. Gen. Virol. 2008, 89, 1036–1042. https://doi.org/10.1099/vir.0.83428-0. PMID: 18343847; PMCID: PMC2885027.
3. de Lima, J.G.S.; Lanza, D.C.F. 2A and 2A-like sequences: Distribution in different virus species and applications in biotechnology. Viruses 2021, 13, 2160. https://doi.org/3390/v13112160. PMID: 34834965; PMCID: PMC8623073.
4. de Lima, J.G.S.; Teixeira, D.G.; Freitas, T.T.; Lima, J.P.M.S.; Lanza, D.C.F. Evolutionary origin of 2A-like sequences in Totiviridae genomes. Virus Res. 2019, 259, 1–9. https://doi.org/1016/j.virusres.2018.10.011. PMID: 30339789.
5. Brown, J.D.; Ryan, M.D. Ribosome “Skipping”: “Stop-Carry On” or “StopGo” Translation. In Recoding: Expansion of Decoding Rules Enriches Gene Expression; Atkins, J.F., Gesteland, R.F., Eds.; Springer: New York, NY, USA, 2010; pp. 101–122.
6. Heras, S.R.; Thomas, M.C.; García-Canadas, M.; de Felipe, P.; García-Perez, J.L.; Ryan, M.D.; Lopez, M.C. L1Tc Non-LTR Retrotransposons from Trypanosoma Cruzi contain a functional viral-like self-cleaving 2A Sequence in frame with the active proteins they encode. Mol. Life Sci. 2006, 63, 1449-1460. https://doi.org/10.1007/s00018-006-6038-2. PMID: 16767356; PMCID: PMC11136212
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8. Luke, G.A.; Ryan, M.D. The 2A story—The end of the beginning. In Beyond the Blueprint—Decoding the Elegance of Gene Expression; Siefi, M., Ed.; InTech: Rijeka, Croatia, 2024; pp 116–145. https://doi.org/10.5772/intechopen.1004928.
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10. Wang, X.; Liu, N.; Wang, F.; Ning, K.; Li, Y.; Zhang, D. Genetic characterization of a novel duck-origin picornavirus with six 2A proteins. Gen. Virol. 2014, 95, 1289–1296. https://doi.org/10.1099/vir.0.063313-0. PMID: 24659102.
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Figure Legends

Figure 1. Supergroup 4 – ‘Paavivirinae’ Viruses not encoding a 2A^NPGP are shown in blue text, those encoding a single copy of 2A^NPGP are shown in black text, whilst those encoding multiple instances are shown in red text.

Figure 2. Schematic (drawn to scale) showing the positions of 2A^NPGP sequences (25aa) within the genome of Aalivirus A1 polyprotein (Panel A). Artificial reporter polyprotein (boxed area) used to programme in vitro Wheat Germ Extract coupled transcription/translation systems together with translation profiles (below). The translation profile from the control FMDV constructs shows three major products: uncleaved [GFP2AGUS] and the cleavage products [GFP2A] and [GUS] whilst the Aalivirus A1 construct shows the two major cleavage products [GFP2A] and [GUS] (Panel B).

1. “Review on Main Arboviruses Circulating on French Guiana, An Ultra-Peripheric European Region in South America”
by Timothee Bonifay, Paul Le Turnier, Yanouk Epelboin, Luisiane Carvalho, Benoit De Thoisy, Félix Djossou, Jean-Bernard Duchemin, Philippe Dussart, Antoine Enfissi, Anne Lavergne et al.
Viruses 2023, 15(6), 1268; https://doi.org/10.3390/v15061268
Available online: https://www.mdpi.com/1999-4915/15/6/1268

2. “An Update on Current Antiviral Strategies to Combat Human Cytomegalovirus Infection”
by Kingshuk Panda, Deepti Parashar and Rajlakshmi Viswanathan
Viruses 2023, 15(6), 1358; https://doi.org/10.3390/v15061358
Available online: https://www.mdpi.com/1999-4915/15/6/1358

3. “Determinants of Chikungunya and O’nyong-Nyong Virus Specificity for Infection of Aedes and Anopheles Mosquito Vectors”
by Solène Cottis, Adrien A. Blisnick, Anna-Bella Failloux and Kenneth D. Vernick
Viruses 2023, 15(3), 589; https://doi.org/10.3390/v15030589
Available online: https://www.mdpi.com/1999-4915/15/3/589

4. “Role of the Microbiome in Aedes spp. Vector Competence: What Do We Know?”
by Qesya Rodrigues Ferreira, Fabian Fellipe Bueno Lemos, Matheus Nascimento Moura, Jéssica Oliveira de Souza Nascimento, Ana Flávia Novaes, Isadora Souza Barcelos, Larissa Alves Fernandes, Liliany Souza de Brito Amaral, Fernanda Khouri Barreto and Fabrício Freire de Melo
Viruses 2023, 15(3), 779; https://doi.org/10.3390/v15030779
Available online: https://www.mdpi.com/1999-4915/15/3/779

5. “Effect of Viral Strain and Host Age on Clinical Disease and Viral Replication in Immunocompetent Mouse Models of Chikungunya Encephalomyelitis”
by Elizabeth J. Anderson, Audrey C. Knight, Mark T. Heise and Victoria K. Baxter
Viruses 2023, 15(5), 1057; https://doi.org/10.3390/v15051057
Available online: https://www.mdpi.com/1999-4915/15/5/1057

6. “Development of Therapeutic Monoclonal Antibodies for Emerging Arbovirus Infections”
by Leonardo F. Ormundo, Carolina T. Barreto and Lilian R. Tsuruta
Viruses 2023, 15(11), 2177; https://doi.org/10.3390/v15112177
Available online: https://www.mdpi.com/1999-4915/15/11/2177

7. “Seroprevalence of IgG Antibodies Directed against Dengue, Chikungunya and West Nile Viruses and Associated Risk Factors in Madagascar, 2011 to 2013”
by Anaïs Broban, Marie-Marie Olive, Michael Luciano Tantely, Anne-Claire Dorsemans, Fanjasoa Rakotomanana, Jean-Pierre Ravalohery, Christophe Rogier, Jean-Michel Heraud and Soa Fy Andriamandimby
Viruses 2023, 15(8), 1707; https://doi.org/10.3390/v15081707
Available online: https://www.mdpi.com/1999-4915/15/8/1707

8. “Deubiquitinating Enzyme Inhibitors Block Chikungunya Virus Replication”
by Lady S. López, Eliana P. Calvo and Jaime E. Castellanos
Viruses 2023, 15(2), 481; https://doi.org/10.3390/v15020481
Available online: https://www.mdpi.com/1999-4915/15/2/481

9. “Serological and Molecular Epidemiology of Chikungunya Virus Infection in Vietnam, 2017–2019”
by Thanh Vu Nguyen, Mya Myat Ngwe Tun, Minh Thang Cao, Huy Manh Dao, Chan Quang Luong, Thi Kim Loan Huynh, Thi Thanh Thuong Nguyen, Thi Nhu Dao Hoang, Kouichi Morita et al.
Viruses 2023, 15(10), 2065; https://doi.org/10.3390/v15102065
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10. “The Innate Immune Response in DENV- and CHIKV-Infected Placentas and the Consequences for the Fetuses: A Minireview”
by Felipe de Andrade Vieira Alves, Priscila Conrado Guerra Nunes, Laíza Vianna Arruda, Natália Gedeão Salomão and Kíssila Rabelo
Viruses 2023, 15(9), 1885; https://doi.org/10.3390/v15091885
Available online: https://www.mdpi.com/1999-4915/15/9/1885

World Hepatitis Day is observed each year on 28 July to raise awareness of viral hepatitis, a type of inflammation of the liver that causes severe liver disease and liver cancer.

The theme for 2025—“Hepatitis: Let’s Break It Down”—calls for urgent action to dismantle the financial, social and systemic barriers, including stigma, that stand in the way of hepatitis elimination and liver cancer prevention.

Chronic hepatitis B and C silently cause liver damage and cancer—despite them being preventable, treatable, and, in the case of hepatitis C, curable. The theme emphasizes the need to simplify, scale up, and integrate hepatitis services—vaccination, safe injection practices, harm reduction and especially testing and treatment—into national health systems.

The campaign is a reminder that we must act now to expand access, integrate care, and end hepatitis as a public health problem by 2030.

In recognition of this important day, we recommend the following related articles, Special Issues, and journals spanning multidisciplinary fields, including clinical medicine. We believe that promoting such research contributes to enhanced public awareness and a greater understanding of viral hepatitis, an inflammation of the liver that causes severe liver disease and liver cancer.

“Curcumin Nanocarriers in the Protection Against Iron- and Alcohol-Induced Oxidative Stress in a Cellular Model of Liver Disease”
by Lucy Petagine, Mohammed G. Zariwala, Satyanarayana Somavarapu, Stefanie Ho Yi Chan and Vinood B. Patel
Biology 2025, 14(5), 455; https://doi.org/10.3390/biology14050455

“Hepatic Estrogen Receptor Alpha Overexpression Protects Against Hepatic Insulin Resistance and MASLD”
by Ester S. Alves, Jessica D. M. Santos, Alessandra G. Cruz, Felipe N. Camargo, Carlos H. Z. Talarico, Anne R. M. Santos, Carlos A. A. Silva, Henrique J. N. Morgan, Sandro L. Matos, Layanne C. C. Araujo et al.
Pathophysiology 2025, 32(1), 1; https://doi.org/10.3390/pathophysiology32010001

“Change in Estimated Glomerular Filtration Rate After Direct-Acting Antiviral Treatment in Chronic Hepatitis C Patients”
by Gantogtokh Dashjamts, Amin-Erdene Ganzorig, Yumchinsuren Tsedendorj, Dolgion Daramjav, Enkhmend Khayankhyarvaa, Bolor Ulziitsogt, Otgongerel Nergui, Ganchimeg Dondov, Tegshjargal Badamjav, Tulgaa Lonjid et al.
Diseases 2025, 13(2), 26; https://doi.org/10.3390/diseases13020026

“Effects of SARS-CoV-2 Spike S1 Subunit on the Interplay Between Hepatitis B and Hepatocellular Carcinoma Related Molecular Processes in Human Liver”
by Giovanni Colonna
Livers 2025, 5(1), 1; https://doi.org/10.3390/livers5010001

“Liver Cancer Neuroscience: Regulating Liver Tumors via Selective Hepatic Vagotomy”
by Kylynda C. Bauer, Shadin Ghabra, Chi Ma Lee Chedester and Tim F. Greten
Methods Protoc. 2024, 7(6), 99; https://doi.org/10.3390/mps7060099

“Role of Circulating microRNAs in Liver Disease and HCC: Focus on miR-122”
by Francesco Colaianni, Veronica Zelli, Chiara Compagnoni, Martina Sara Miscione, Mario Rossi, Davide Vecchiotti, Monica Di Padova, Edoardo Alesse, Francesca Zazzeroni and Alessandra Tessitore
Genes 2024, 15(10), 1313; https://doi.org/10.3390/genes15101313

“Impact of Hepatitis Delta Virus Infection on the Selection of Hepatitis B Surface Antigen Mutations”
by Kabo Baruti,Wonderful T. Choga, Bonolo B. Phinius, Basetsana Phakedi, Lynnette Bhebhe, Gorata G. A. Mpebe, Patience C. Motshosi, Tsholofelo Ratsoma, Sikhulile Moyo, Mosimanegape Jongman et al.
Genes 2024, 15(8), 982; https://doi.org/10.3390/genes15080982

“NAFLD/MASLD and the Gut–Liver Axis: From Pathogenesis to Treatment Options”
by Natalia G. Vallianou, Dimitris Kounatidis, Sotiria Psallida, Nikolaos Vythoulkas-Biotis, Andreas Adamou, Tatiana Zachariadou, Sofia Kargioti, Irene Karampela and Maria Dalamaga
Metabolites 2024, 14(7), 366; https://doi.org/10.3390/metabo14070366

“miRNA Expression and HCC Occurrence in HCV Cirrhotic Patients Treated with Direct Acting Antivirals”
by Antonietta Romano, Alessandra Brocca, Zoe Mariño, Sofía Pérez-del-Pulgar, Sabela Lens, Loreto Boix, María Reig, Jordi Bruix, Giulio Ceolotto, Valeria Calvino et al.
Livers 2024, 4(2), 275-286; https://doi.org/10.3390/livers4020020

“The Full-Genome Analysis and Generation of an Infectious cDNA Clone of a Genotype 6 Hepatitis E Virus Variant Obtained from a Japanese Wild Boar: In Vitro Cultivation in Human Cell Lines”
by Putu Prathiwi Primadharsini, Masaharu Takahashi, Tsutomu Nishizawa, Yukihiro Sato, Shigeo Nagashima, Kazumoto Murata and Hiroaki Okamoto
Viruses 2024, 16(6), 842; https://doi.org/10.3390/v16060842

“Hepatitis C Prevalence and Birth Outcomes among Pregnant Women in the United States: A 2010–2020 Population Study”
by Paul Wasuwanich, Songyos Rajborirug, Robert S. Egerman, Tony S. Wen and Wikrom Karnsakul
Pathogens 2024, 13(4), 321; https://doi.org/10.3390/pathogens13040321

“Prospects for Controlling Hepatitis B Globally”
by Vicente Soriano, Víctor Moreno-Torres, Ana Treviño, Fernando de Jesús, Octavio Corral and Carmen de Mendoza
Pathogens 2024, 13(4), 291; https://doi.org/10.3390/pathogens13040291

“Longterm Outcome of Therapeutic Vaccination with a Third Generation Pre-S/S HBV Vaccine (PreHevbrioR) of Chronically HBV Infected Patients”
by Hedwig Roggendorf, Daniel Shouval, Michael Roggendorf and Guido Gerken
J. Pers. Med. 2024, 14(4), 364; https://doi.org/10.3390/jpm14040364

“NAFLD Fibrosis Progression and Type 2 Diabetes: The Hepatic–Metabolic Interplay”
by Simona Cernea
Life 2024, 14(2), 272; https://doi.org/10.3390/life14020272

“Updated Clinical Guidelines on the Management of Hepatitis C Infection in Children”
by Chaowapong Jarasvaraparn, Christopher Hartley and Wikrom Karnsakul
Pathogens 2024, 13(2), 180; https://doi.org/10.3390/pathogens13020180

“Non-Invasive Assessment of Liver Fibrosis in Hepatitis B Patients”
by Chinmay Bera, Nashla Hamdan-Perez and Keyur Patel
J. Clin. Med. 2024, 13(4), 1046; https://doi.org/10.3390/jcm13041046

“Real-World Utilization of Corticosteroids in Severe Alcoholic Hepatitis: Eligibility, Response, and Outcomes”
by Ana-Maria Singeap, Horia Minea, Oana Petrea, Madalina-Andreea Robea, Ioana-Miruna Balmuș, Raluca Duta, Ovidiu-Dumitru Ilie, Carmen Diana Cimpoesu, Carol Stanciu and Anca Trifan
Medicina 2024, 60(2), 311; https://doi.org/10.3390/medicina60020311

“Autoimmune Hepatitis: A Diagnostic and Therapeutic Overview”
by Lydia A. Mercado, Fernando Gil-Lopez, Razvan M. Chirila and Denise M. Harnois
Diagnostics 2024, 14(4), 382; https://doi.org/10.3390/diagnostics14040382

“Hepatoprotective Effects of Flavonoids against Benzo[a]Pyrene-Induced Oxidative Liver Damage along Its Metabolic Pathways”
by Min Kim, Seung-Cheol Jee and Jung-Suk Sung
Antioxidants 2024, 13(2), 180; https://doi.org/10.3390/antiox13020180

”Enhancing Liver Delivery of Gold Nanoclusters via Human Serum Albumin Encapsulation for Autoimmune Hepatitis Alleviation”
by Cong Meng, Yu Liu, Yuping Ming, Cao Lu, Yanggege Li, Yulu Zhang, Dongdong Su, Xueyun Gao and Qing Yuan
Pharmaceutics 2024, 16(1), 110; https://doi.org/10.3390/pharmaceutics16010110

“Hepatitis B Virus Reactivation with Immunosuppression: A Hidden Threat?”
by Sama Anvari and Keith Tsoi
J. Clin. Med. 2024, 13(2), 393; https://doi.org/10.3390/jcm13020393

“Metabolic Dysfunction-Associated Fatty Liver Disease and Chronic Viral Hepatitis: The Interlink”
by Cornelius J. Fernandez, Mohammed Alkhalifah, Hafsa Afsar and Joseph M. Pappachan
Pathogens 2024, 13(1), 68; https://doi.org/10.3390/pathogens13010068

“A Case Report: Idiopathic or Drug-Induced Autoimmune Hepatitis—Can We Draw a Line?”
by Dorotea Božić, Ante Tonkić, Jr,Katarina Vukojevic and Maja Radman
Clin. Pract. 2023, 13(6), 1393–1399; https://doi.org/10.3390/clinpract13060125

“Liver dECM–Gelatin Composite Bioink for Precise 3D Printing of Highly Functional Liver Tissues”
by Min Kyeong Kim, Wonwoo Jeong and Hyun-Wook Kang
J. Funct. Biomater. 2023, 14(8), 417; https://doi.org/10.3390/jfb14080417

“Viral Hepatitis: Diagnosis, Treatment and Management” Guest Editors: Dr. Veysel Tahan and Dr. Resat Ozaras Submission deadline: 31 August 2025	“New Insights into Diagnosis and Therapeutic Strategies for Chronic Liver Diseases” Guest Editor: Prof. Dr. Cristina Marginean Submission deadline: 20 October 2025
“The Surveillance, Prevention, and Treatment of Viral Hepatitis: Looking Forward to Global Elimination” Guest Editor: Dr. Melanie Deutsch Submission deadline: 31 October 2025	“Viral Hepatitis and Therapeutic Strategies” Guest Editor: Dr. Arshi Khanam Submission deadline: 20 November 2025
“Genetic Analysis of Hepatitis Virus Infection” Guest Editors: Prof. Dr. Dan Florin Mihǎilescu and Dr. Maria Alexandra Mernea Submission deadline: 20 November 2025	“Oxidative Stress in Hepatic Diseases” Guest Editor: Dr. Miquel Mulero Submission deadline: 21 November 2025
“Viral Hepatitis Among Specific Populations: Epidemiology, Transmission, Treatment, and Prevention” Guest Editor: Dr. Aldemir B. Oliveira-Filho Submission deadline: 15 December 2025	“Biology of Liver Diseases” Guest Editors: Dr. Tadashi Namisaki and Dr. Hiroaki Takaya Submission deadline: 20 December 2025
“Hepatitis E Virus (HEV) Infection Among Humans and Animals: Epidemiology, Clinical Characteristics, Treatment and Prevention—2nd Edition” Guest Editors: Dr. Jelena Prpić and Dr. Magdalena Baymakova Submission deadline: 31 December 2025	“Human Hepatitis Viruses and Their Animal Homologues” Guest Editors: Dr. Bo Wang and Prof. Dr. Xinglou Yang Submission deadline: 31 December 2025
“Advances in Hepatitis: Prevention, Treatment, and Global Health Impact” Guest Editors: Dr. Michał Brzdęk, Prof. Dr. Dorota Zarębska-Michaluk and Dr. Krystyna Dobrowolska Submission deadline: 28 January 2026	“Pathogenesis of Viral Hepatitis” Guest Editor: Dr. Po-Yuan Ke Submission deadline: 28 February 2026
“Liver Diseases: Diagnosis and Treatment in the Era of Personalized Medicine” Guest Editors: Dr. María Teresa Arias-Loste and Dr. Armando Raúl Guerra-RuizSubmission deadline: 30 April 2026	“Gastrointestinal and Liver Diseases: New Advances in Diagnosis and Prognosis” Guest Editor: Prof. Dr. Carmen Fierbinteanu-Braticevici Submission deadline: closed (31 December 2023)

Conference: The 12th China Veterinary Conference
Date: 21 August–24 August 2025
Location: Xi’an, China

We are pleased to announce that MDPI will be participating in the 12th China Veterinary Conference in Xi’an, China, from 21 August to 24 August 2025.

The China Veterinary Congress is a large-scale conference held for all livestock and veterinary practitioners across the country. Its purpose is to enhance the overall quality of livestock health during breeding, animal disease prevention and control, animal disease diagnosis and treatment, and veterinary public health in China. The 2024 Livestock and Veterinary Products Exhibition has also been held concurrently to this conference. Since 2010, the China Veterinary Congress has successfully held eleven sessions, providing a platform for experts to conduct lectures, a display stage for enterprises, and a learning platform for the audience. The Congress has become a comprehensive and integrated platform that combines learning, communication, display, training, and competition.

The following MDPI journals will be represented at the conference:

• Animals;
• Veterinary Sciences;
• Viruses;
• Bacteria;
• JDB;
• Parasitologia;
• Pets;
• Poultry.

If you are planning to attend the conference, please feel free to start a conversation with us. We invite all attendees to visit MDPI’s booth and meet with our esteemed Editorial Board Members who will be present.

1. “Characterization of a Novel African Swine Fever Virus p72 Genotype II from Nigeria”
by Aruna Ambagala, Kalhari Goonewardene, Lindsey Lamboo, Melissa Goolia, Cassidy Erdelyan, Mathew Fisher, Katherine Handel, Oliver Lung, Sandra Blome, Jacqueline King et al.
Viruses 2023, 15(4), 915; https://doi.org/10.3390/v15040915
Available online: https://www.mdpi.com/1999-4915/15/4/915

2. “A Spontaneously Occurring African Swine Fever Virus with 11 Gene Deletions Partially Protects Pigs Challenged with the Parental Strain”
by Tomoya Kitamura, Kentaro Masujin, Reiko Yamazoe, Ken-ichiro Kameyama, Mizuki Watanabe, Mitsutaka Ikezawa, Manabu Yamada and Takehiro Kokuho
Viruses 2023, 15(2), 311; https://doi.org/10.3390/v15020311
Available online: https://www.mdpi.com/1999-4915/15/2/311

3. “African Swine Fever Virus Interaction with Host Innate Immune Factors”
by Ayoola Ebenezer Afe, Zhao-Ji Shen, Xiaorong Guo, Rong Zhou and Kui Li
Viruses 2023, 15(6), 1220; https://doi.org/10.3390/v15061220
Available online: https://www.mdpi.com/1999-4915/15/6/1220

4. “Point-of-Care Testing for Sensitive Detection of the African Swine Fever Virus Genome”
by Ahmed Elnagar, Sandra Blome, Martin Beer and Bernd Hoffmann
Viruses 2022, 14(12), 2827; https://doi.org/10.3390/v14122827
Available online: https://www.mdpi.com/1999-4915/14/12/2827

5. “I329L: A Dual Action Viral Antagonist of TLR Activation Encoded by the African Swine Fever Virus (ASFV)”
by Sílvia Correia, Pedro Luís Moura, Sónia Ventura, Alexandre Leitão and Robert Michael Evans Parkhouse
Viruses 2023, 15(2), 445; https://doi.org/10.3390/v15020445
Available online: https://www.mdpi.com/1999-4915/15/2/445

6. “The Long-Jumping of African Swine Fever: First Genotype II Notified in Sardinia, Italy”
by Silvia Dei Giudici, Federica Loi, Sonia Ghisu, Pier Paolo Angioi, Susanna Zinellu, Mariangela Stefania Fiori, Francesca Carusillo, Diego Brundu, Giulia Franzoni, Giovanni Maria Zidda et al.
Viruses 2024, 16(1), 32; https://doi.org/10.3390/v16010032
Available online: https://www.mdpi.com/1999-4915/16/1/32

7. “Functional Landscape of African Swine Fever Virus–Host and Virus–Virus Protein Interactions”
by Katarzyna Magdalena Dolata, Gang Pei, Christopher L. Netherton and Axel Karger
Viruses 2023, 15(8), 1634; https://doi.org/10.3390/v15081634
Available online: https://www.mdpi.com/1999-4915/15/8/1634

8. “Developing an Indirect ELISA for the Detection of African Swine Fever Virus Antibodies Using a Tag-Free p15 Protein Antigen”
by Zhi Wu, Huipeng Lu, Dewei Zhu, Jun Xie, Fan Sun, Yan Xu, Hua Zhang, Zhijun Wu, Wenlong Xia and Shanyuan Zhu
Viruses 2023, 15(9), 1939; https://doi.org/10.3390/v15091939
Available online: https://www.mdpi.com/1999-4915/15/9/1939

9. “Mammalian Cell-Line-Expressed CD2v Protein of African Swine Fever Virus Provides Partial Protection against the HLJ/18 Strain in the Early Infection Stage”
by Rong-Hong Hua, Jing Liu, Shu-Jian Zhang, Ren-Qiang Liu, Xian-Feng Zhang, Xi-Jun He, Dong-Ming Zhao and Zhi-Gao Bu
Viruses 2023, 15(7), 1467; https://doi.org/10.3390/v15071467
Available online: https://www.mdpi.com/1999-4915/15/7/1467

10. “Evaluation of the Deletion of the African Swine Fever Virus Gene O174L from the Genome of the Georgia Isolate”
by Elizabeth Ramirez-Medina, Lauro Velazquez-Salinas, Ayushi Rai, Nallely Espinoza, Alyssa Valladares, Ediane Silva, Leeanna Burton, Edward Spinard, Amanda Meyers, Guillermo Risatti et al.
Viruses 2023, 15(10), 2134; https://doi.org/10.3390/v15102134
Available online: https://www.mdpi.com/1999-4915/15/10/2134