Review
Virology
Rachel A. Reyna, Scott C. Weaver
Summary: Eastern (EEEV), Venezuelan (VEEV), and western equine encephalitis viruses (WEEV) are mosquito-borne alphaviruses that cause febrile illness and severe encephalitic disease. The lack of vaccines and therapeutics highlights the need for advanced animal models and detailed mechanistic understanding of the neurological sequelae induced by these viruses. This review summarizes the clinical neurologic findings, available animal models, and the importance of developing therapeutics and vaccines.
Article
Biochemistry & Molecular Biology
Pei-Tzu Huang, Sirle Saul, Shirit Einav, Christopher R. M. Asquith
Summary: This study presented a series of lead compounds targeting DENV and VEEV with promising results, demonstrating activity against both viruses. These compounds have the potential to be developed into clinical drugs for combating DENV, VEEV, and potentially other emerging viral threats.
Review
Virology
Tyler J. Ogorek, Jennifer E. Golden
Summary: Venezuelan, western, and eastern equine encephalitic alphaviruses (VEEV, WEEV, and EEEV) are highly pathogenic arboviruses that cause significant harm to equines and humans. Currently, there are no approved vaccines or therapeutics for general use to mitigate alphavirus infections. The review focuses on small molecule inhibitors of VEEV, WEEV, and EEEV that have been identified or advanced in the last five years, highlighting milestone data and key considerations for compound development.
Article
Virology
Amanda L. Phelps, Francisco J. Salguero, Laura Hunter, Alexander L. Stoll, Dominic C. Jenner, Lyn M. O'Brien, E. Diane Williamson, M. Stephen Lever, Thomas R. Laws
Summary: Venezuelan equine encephalitis virus (VEEV) causes a disease characterized by systemic infection and sometimes severe encephalitis in humans. In a mouse model, biomarkers related to inflammation were identified and found to be strongly correlated with disease severity. The virus was found in various regions of the brain, and the olfactory bulb and midbrain/thalamus showed the most pathology. Targeting these biomarkers may help improve the encephalitic syndrome caused by VEEV.
Article
Virology
Bibha Dahal, Caitlin W. Lehman, Ivan Akhrymuk, Nicole R. Bracci, Lauren Panny, Michael D. Barrera, Nishank Bhalla, Jonathan L. Jacobs, Jonathan D. Dinman, Kylene Kehn-Hall
Summary: The research revealed that the loss of PERK significantly reduced VEEV and EEEV infectious titers in human primary astrocytes, pericytes, and endothelial cells. Moreover, PERK depletion also affected nonstructural protein translation and RNA production of various RNA viruses, suggesting that PERK is a potential target for antiviral drug development.
Review
Microbiology
Anthony Torres-Ruesta, Rhonda Sin-Ling Chee, Lisa F. P. Ng
Summary: Alphaviruses are mosquito-borne pathogens that can cause a wide range of symptoms, including arthritis and encephalitis. Susceptible populations historically develop long-lasting antibody responses after large outbreaks, indicating the potential for vaccines. However, little is known about humoral responses triggered by other emerging alphaviruses, which is crucial for improving diagnostics and vaccine development.
Article
Pharmacology & Pharmacy
Ya-Nan Zhang, Hong-Qing Zhang, Gui-Feng Wang, Zhe-Rui Zhang, Jia-Qi Li, Xiao-Ling Chen, Yan-Yan Hu, Xiang-Yue Zeng, Yu-Jia Shi, Jing Wang, Ying-Hua Li, Xiao-Dan Li, Chun-He Wang, Bing Zhu, Bo Zhang
Summary: The Omicron variant demonstrates immune escape potential through spike protein mutations, necessitating the urgent need for broad-spectrum prevention strategies. Researchers developed a cost-effective platform using a modified VEEV replicon to deliver replicating mRNA encoding the neutralizing antibody 3E8, demonstrating its feasibility and protective efficacy against Omicron infection in hamsters. This platform offers a safe and efficient approach for preventing SARS-CoV-2.
ANTIVIRAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Lulu Han, Shuai Song, Huilin Feng, Wenqiang Wei, Fusheng Si
Summary: Venezuelan equine encephalitis (VEE) is a serious zoonotic disease caused by the VEE virus, posing a major threat to both humans and animals. The lack of licensed vaccines or drugs for human use against VEEV has prompted extensive research on vaccine development. This paper provides an overview of VEEV and its infection mechanism, introduces the available vaccine types, and highlights the challenges and potential strategies for vaccine development.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Immunology
Na Li, Xiao-Ling Chen, Qi Li, Zhe-Rui Zhang, Cheng-Lin Deng, Bo Zhang, Xiao-Dan Li, Han-Qing Ye
Summary: This study establishes a more convenient and efficient method for rapid screening of inhibitors blocking syncytium formation using VEEV-SARS-CoV-2-S-eGFP replicating cells. The assay can be performed in a BSL-2 laboratory without manipulation of live SARS-CoV-2.
EMERGING MICROBES & INFECTIONS
(2022)
Article
Infectious Diseases
Roelof van Ewijk, Minke H. W. Huibers, Meindert E. Manshande, Ginette M. Ecury-Goossen, Ashley J. Duits, Job C. Calis, Aleid G. Van Wassenaer-Leemhuis
Summary: In this prospective observational study of infants infected with chikungunya before the age of 6 months during the 2014-2015 epidemic in Curacao, Dutch Antilles, a high percentage of developmental problems were observed two years post-infection. Further studies are needed to assess causality and preventive measures should include young infants infected in early infancy.
BMC INFECTIOUS DISEASES
(2021)
Article
Microbiology
Nicole N. Haese, Nicholas A. May, Sharon Taft-Benz, Omar Moukha-Chafiq, Nikhil Madadi, Sixue Zhang, Shuklendu D. Karyakarte, Kevin J. Rodzinak, Theresa H. Nguyen, Michael Denton, Aaron D. Streblow, Nichole A. Towers, Lynn Rasmussen, Robert J. Bostwick, Joseph A. Maddry, Subramaniam Ananthan, Corinne E. Augelli-Szafran, Mark J. Suto, Wes Sanders, Nathaniel Moorman, Victor DeFilippis, Mark T. Heise, Ashish K. Pathak, Daniel N. Streblow, Thomas E. Morrison
Summary: A quinolinone compound was found to have antiviral activity against VEEV and other alphaviruses, inhibiting the early-to-mid stage of viral replication. Deep sequencing and reverse genetics studies identified unique resistance mutations in the nsP2 gene that conferred VEEV resistance on this chemical series, while computational modeling indicated potential docking alignment for the compounds.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Hisham A. Imad, Wasin Matsee, Sajikapon Kludkleeb, Punyisa Asawapaithulsert, Juthamas Phadungsombat, Emi E. Nakayama, Keita Suzuki, Pornsawan Leaungwutiwong, Watcharapong Piyaphanee, Weerapong Phumratanaprapin, Tatsuo Shioda
Summary: Chikungunya virus is a mosquito-borne alphavirus that can cause fever, arthralgia, and rash. Diagnosis is challenging as symptoms can overlap with other viruses, causing a dilemma for clinicians. The virus can lead to post-chikungunya arthritis in the chronic phase, affecting patients' daily living activities.
TROPICAL MEDICINE AND INFECTIOUS DISEASE
(2021)
Article
Microbiology
Xiang Liu, Yee-Suan Poo, Juliana C. Alves, Roque P. Almeida, Helen Mostafavi, Patrick Chun Hean Tang, Richard Bucala, Mauro M. Teixeira, Adam Taylor, Ali Zaid, Suresh Mahalingam
Summary: CHIKV has been prevalent in Africa, Asia, and the Indian Ocean Islands for decades. There are currently no clinically approved vaccines or specific antiviral drugs targeting CHIKV. The upregulation of IL-17 detected in CHIKV disease patients and the reduced disease seen in IL-17-deficient mice suggest a correlation between IL-17 signaling pathways and CHIKV-induced arthritic inflammation. With an established role in contributing to the pathogenesis of immune-mediated diseases, such as psoriatic arthritis and rheumatoid arthritis, IL-17 signaling plays an important role in alphavirus arthritides.
Article
Multidisciplinary Sciences
Rhian Jones, Gabriel Bragagnolo, Rocio Arranz, Juan Reguera
Summary: Positive-sense single-stranded RNA viruses, such as coronaviruses, flaviviruses and alphaviruses, replicate and transcribe within virus-induced membranous organelles in host cells. The remodeling of host-cell membranes for organelle formation allows concentration of metabolites and proteins for viral RNA synthesis, while preventing detection by the cellular innate immune system. The structure of non-structural protein 1 (nsP1) of the alphavirus chikungunya virus reveals the mechanism of RNA capping and membrane binding, providing insights into viral replication complex formation and potential antiviral strategies.
Article
Virology
Lukasz Kedzierski, Abigail Er Qi Tan, Isabelle Jia Hui Foo, Sandra E. Nicholson, John K. Fazakerley
Summary: SOCS5 plays a crucial role in regulating anti-viral immunity in the brain, influencing the critical balance between immunopathology and virus persistence, thus affecting the pathogenesis and clinical outcomes of neurotropic virus infections.