Article
Chemistry, Multidisciplinary
Pradeep Chopra, Tejabhiram Yadavalli, Francesco Palmieri, Seino A. K. Jongkees, Luca Unione, Deepak Shukla, Geert-Jan Boons
Summary: Inhibition of human heparanase (Hpse) has been found to be a promising therapeutic strategy for preventing the spread of herpes simplex virus (HSV-1). The synthesis of hexa- and octasaccharide inhibitors of Hpse showed potent enzyme inhibition and the presence of 2-O-sulfation on iduronic acid was tolerated. These inhibitors not only blocked viral-induced shedding of cell-surface heparan sulfate (HS) but also inhibited cell migration and proliferation in corneal epithelial cells infected with HSV-1.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Oncology
Hayle Scanlan, Zachary Coffman, Jeffrey Bettencourt, Timothy Shipley, Debra E. Bramblett
Summary: This review provides an overview of HSV-1 as an oncolytic virus candidate and the genomic organization of T-VEC. The advantages and limitations of T-VEC compared to other HSV-1 oncolytic virus variants currently in clinical trials are discussed. Additionally, future directions for the use of HSV-1 oncolytic viruses as cancer therapy are explored.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Rahul K. Suryawanshi, Chandrashekhar D. Patil, Alex Agelidis, Raghuram Koganti, Tejabhiram Yadavalli, Joshua M. Ames, Hemant Borase, Deepak Shukla
Summary: This study found that compared to animals lacking HPSE, wild-type mice exhibit notable pathophysiology during HSV-1 reinfection. HPSE promotes infected cell survival and supports the formation of a pro-disease environment. In contrast, lack of HPSE enhances intrinsic immunity by promoting cytokine expression, inducing necroptosis of infected cells, and decreasing leukocyte infiltration into the cornea. Overall, recent prior infection immunity fails to abolish disease manifestation during HSV-1 reinfection unless HPSE is rendered inactive.
Article
Immunology
Shuyong Zhu, Abel Viejo-Borbolla
Summary: HSV-1 and HSV-2 are two of the most prevalent human viruses worldwide, causing a variety of diseases. Immune responses play a key role in controlling HSV, but the virus has developed mechanisms to evade them. The severity of disease upon HSV infection varies among individuals, partly due to genetic polymorphisms. HSV has lytic and latent replication cycles, with the latter leading to disease.
Article
Pharmacology & Pharmacy
Hiroki Kondo, Tetsuo Koshizuka, Ryuichi Majima, Keita Takahashi, Ken Ishioka, Tatsuo Suzutani, Naoki Inoue
Summary: The compound 147B3 has shown efficacy in inhibiting HCMV and HSV-1 infection, potentially by targeting viral transactivators through their interaction with factors required for the viral gene expression system.
ANTIVIRAL RESEARCH
(2021)
Article
Microbiology
Kevin Danastas, Gerry Guo, Jessica Merjane, Nathan Hong, Ava Larsen, Monica Miranda-Saksena, Anthony L. Cunningham
Summary: This study explores the effects of interferons (IFNs) on herpes simplex virus-1 (HSV-1) and reveals that IFNs have the potential to block virus release from nerve endings, thereby preventing transmission into the skin. The study also highlights the potential wider antiviral effects of IFN-γ in neurons, suggesting its role in HSV-1 reactivation. These findings identify new targets for the development of immunotherapies to impede HSV-1 spread from nerves to the skin.
Article
Virology
Tejabhiram Yadavalli, Pankaj Sharma, David Wu, Divya Kapoor, Deepak Shukla
Summary: CREB3 plays a key role in HPSE-facilitated HSV-1 egress. HPSE expression is correlated with CREB3 expression, and HPSE-transfected cells show higher CREB3 expression, while HPSE knockout cells show lower CREB3 expression. CREB3-transfected cells exhibit significantly increased export of HPSE upon infection. Additionally, COPII, which mediates HPSE trafficking, is upregulated via a CREB3-dependent pathway during HSV-1 infection. Co-transfection of CREB3 and HPSE results in the highest viral release.
Article
Microbiology
Jie Wang, Kun-Te Shang, Qiong-Hong Ma, Zhao-Ying Dong, Yi-Hong Chen, Yu-Feng Yao
Summary: This study aimed to determine whether HSV-1 can be transmitted through TNTs and to investigate the effect of inhibiting the Arp2/3 complex on the intercellular transmission of HSV-1. The results showed that HSV-1 can be transmitted through TNTs and that inhibiting the Arp2/3 complex reduces the number of TNTs and the spread of HSV-1. This finding provides new insights into the transmission mode of HSV-1 and suggests a potential new antiviral target.
Review
Virology
Yijing Chen, Wen Liu, Bing Luo
Summary: This article summarizes the glycosylation of herpes virus envelope glycoproteins and its impact on viral infection, as well as the use of glycosylation inhibitors.
Article
Immunology
Mette Ratzer Freytag, Sofie Eg Jorgensen, Michelle Molgaard Thomsen, Ali Al-Mousawi, Alon Schneider Hait, David Olagnier, Jakob T. Bay, Marie Helleberg, Trine H. Mogensen
Summary: This study describes a 19-year-old woman with systemic HSV-1 infection and HLH, as well as a fatal course of neonatal herpesvirus infection postpartum. Investigation showed impaired antiviral responses in the mother's cells, potentially caused by variants in CASP8 or other noncoding regions of the genome.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Microbiology
Max E. Mertens, David M. Knipe
Summary: Cells activate DNA damage response when infected by DNA viruses such as herpes simplex virus 1, with different DDR kinase pathways in infected and uninfected cells. Key host gene products and DDR components have opposite effects on the replication of herpes simplex virus 1, suggesting the virus manipulates the host cell DDR to facilitate its replication while deactivating antiviral aspects.
Article
Biochemistry & Molecular Biology
Bishajit Sarkar, Md. Asad Ullah, Yusha Araf, Sowmen Das, Md. Hasanur Rahman, Abu Tayab Moin
Summary: HSV is a highly infectious virus with two types, HSV-1 and HSV-2, infecting millions worldwide. This study designed three polyvalent subunit vaccines targeting multiple strains of HSV, which showed stability and potential effectiveness through molecular docking and simulation studies. Validation of these vaccines in wet lab-based studies is still needed.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Microbiology
Ye Liu, Qiao You, Fang Zhang, Deyan Chen, Zhenping Huang, Zhiwei Wu
Summary: Harringtonine (HT) significantly inhibited HSV-1 infection and two ACV-resistant strains by mainly targeting HVEM and reducing the early stage of HSV-1 infection. The study demonstrated that HT could be a promising therapeutic candidate for mitigating HSV-1-induced pathogenesis.
FRONTIERS IN MICROBIOLOGY
(2021)
Review
Virology
Hemant Borase, Deepak Shukla
Summary: This review summarizes the pathogenesis of HSV-2 and its cellular interactions, explores new strategies and challenges in regulating HSV-2 replication and influencing the cell cycle through host cellular components, and presents a fresh perspective on the treatment of HSV-2 by targeting cellular proteins and pathways.
Article
Biochemistry & Molecular Biology
Pu Huang, Xu Wang, Mengyue Lei, Ying Ma, Hongli Chen, Jing Sun, Yunzhang Hu, Jiandong Shi
Summary: This study investigates the metabolic interaction between host cells and HSV-1. By analyzing the metabolic profiles in HSV-1-infected lung fibroblasts, the researchers found that HSV-1 induces metabolic reprogramming in host cells to promote or resist viral replication. They confirmed that the addition of the tryptophan metabolite kynurenine promotes viral replication, while the addition of 25-Hydroxycholesterol inhibits replication. Additionally, HSV-1 replication was enhanced in choline metabolic rate-limiting enzyme-deficient mouse macrophages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Cell Biology
Chandrashekhar D. Patil, Deepak Shukla
Summary: Very little is known about the mechanisms that restrict neurotropic herpesviruses from infecting the central nervous system and causing neuron death. However, recent research has shown that OPTN-mediated autophagy acts as an intrinsic immune barrier against these viruses and protects the CNS from neurodegenerative stress.
Article
Pharmacology & Pharmacy
Rahul K. Suryawanshi, Chandrashekhar D. Patil, David Wu, Pritam Kumar Panda, Sudhanshu Kumar Singh, Ipsita Volety, Rajeev Ahuja, Yogendra Kumar Mishra, Deepak Shukla
Summary: In this study, a small molecule called BX795 was discovered as a potential antiviral drug that can directly interact with the host factor protein kinase C (PKC) to reduce viral replication. This finding sheds light on a previously unknown mechanism by which BX795 exerts its antiviral potential.
ANTIVIRAL RESEARCH
(2022)
Review
Virology
Pankaj Sharma, Divya Kapoor, Deepak Shukla
Summary: This article discusses the role of HPSE and SDC-1 as newly identified host factors that facilitate HSV-1 release during infection.
Article
Microbiology
Chandrashekhar D. Patil, Rahul K. Suryawanshi, Divya Kapoor, Deepak Shukla
Summary: HSV-1 infection induces significant alterations in host metabolism, limiting the energy and macromolecular precursors required for viral replication. This study is of great importance for understanding the pathogenesis of HSV-1 infection.
Review
Biochemistry & Molecular Biology
Hester van Mourik, Mengying Li, Sabine Baumgartner, Jan Theys, Ronit Shiri-Sverdlov
Summary: Cathepsins are lysosomal proteases that play an essential role in maintaining cellular homeostasis and are involved in various physiological processes. They have been linked to pathologies such as NASH and HCC. Although the information regarding their involvement in NASH-HCC is limited, there is accumulating evidence supporting their role in both NASH and HCC. Given their role in both conditions, it is likely that Cathepsins play a more significant role in the transition from NASH to HCC, compared to HCC derived from other causes. This review provides an overview of the available data on Cathepsins in NASH and HCC, and highlights therapeutic options in this context.
Review
Biochemistry & Molecular Biology
James Elste, Angelica Chan, Chandrashekhar Patil, Vinisha Tripathi, Daniel M. Shadrack, Dinesh Jaishankar, Andrew Hawkey, Michelle Swanson Mungerson, Deepak Shukla, Vaibhav Tiwari
Summary: The structural diversity of heparan sulfate (HS) in various vertebrates and invertebrates is remarkably preserved and plays a key role in ligand binding and virus entry. The interaction between glycoprotein D (gD) from herpes simplex virus (HSV) and 3-O sulfated HS leads to virus-cell fusion and HSV entry. HSV-1, which infects a large number of people worldwide, can also cause severe diseases in both primates and non-primates. The enzymatic modification of HS by 3-O sulfotransferase-3 (3-OST-3) enhances HSV-1 infectivity and suggests a possible role of HS in cross-species transmission.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Review
Microbiology
Divya Kapoor, Deepak Shukla
Summary: Neutrophil extracellular traps (NETs) are net-like structures released from neutrophils mainly containing cell-free DNA decorated with histones and neutrophil granule proteins. NETs can be induced by various stimuli such as pathogens, cytokines, and immune complexes. They have both beneficial and detrimental effects in capturing pathogens and aggravating inflammation. This review focuses on the formation mechanism of NETs in different ocular pathologies, particularly highlighting their potential implications during herpes simplex virus (HSV) ocular infections and as prospective targets for ocular disease treatment.
Review
Biochemistry & Molecular Biology
Annemarie J. F. Westheim, Lara M. Stoffels, Ludwig J. Dubois, Jeroen van Bergenhenegouwen, Ardy van Helvoort, Ramon C. J. Langen, Ronit Shiri-Sverdlov, Jan Theys
Summary: Cancer burden is increasing rapidly globally, with lifestyle factors such as unhealthy diet being major contributors. The specific fatty acids that contribute to a healthy and balanced diet in terms of cancer risk and prognosis are still unclear. This review explores the associations between intake of different fatty acids and cancer risk, as well as the effects of specific fatty acids on tumor cells and inflammation-induced cancer progression, highlighting challenges and opportunities for fatty acid tailored nutritional interventions.
Article
Multidisciplinary Sciences
Rahul K. Suryawanshi, Chandrashekhar D. Patil, Alex Agelidis, Raghuram Koganti, Tejabhiram Yadavalli, Joshua M. Ames, Hemant Borase, Deepak Shukla
Summary: This study found that compared to animals lacking HPSE, wild-type mice exhibit notable pathophysiology during HSV-1 reinfection. HPSE promotes infected cell survival and supports the formation of a pro-disease environment. In contrast, lack of HPSE enhances intrinsic immunity by promoting cytokine expression, inducing necroptosis of infected cells, and decreasing leukocyte infiltration into the cornea. Overall, recent prior infection immunity fails to abolish disease manifestation during HSV-1 reinfection unless HPSE is rendered inactive.
Article
Medicine, Research & Experimental
Tejabhiram Yadavalli, Sudhanshu Kumar Singh, Abhijit A. Date, Deepak Shukla
Summary: This study evaluated the acute and short-term toxicity of orally administered BX795 in mice, as well as its pharmacokinetics and tissue distribution. The results showed that orally administered BX795 was well tolerated, had an oral bioavailability of 56%, and reached ocular and genital tissues within the first 15 min of dosing. The study indicated that orally administered BX795 can significantly reduce herpesvirus replication in ocular and genital tissue.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Virology
Hemant Borase, Deepak Shukla
Summary: This review summarizes the pathogenesis of HSV-2 and its cellular interactions, explores new strategies and challenges in regulating HSV-2 replication and influencing the cell cycle through host cellular components, and presents a fresh perspective on the treatment of HSV-2 by targeting cellular proteins and pathways.
Article
Microbiology
Ilina Bhattacharya, Ipsita Volety, Deepak Shukla
Summary: Tank-binding kinase 1 (TBK1) plays a crucial role in defending against herpes simplex virus type 1 (HSV-1), and the interplay between OPTN, TBK1, and autophagy significantly impacts the outcome of HSV-1 infection.
