Article
Virology
Kelly S. Harrison, Nishani Wijesekera, Anastasia G. J. Robinson, Vanessa C. Santos, Robert H. Oakley, John A. Cidlowski, Clinton Jones
Summary: This study suggests that female mice expressing GR(S229A) have significantly lower levels of infectious virus during explant-induced reactivation compared to male GR(S229A) or wild-type mice. Furthermore, female GR(S229A) mice have fewer VP16 + TG neurons during the early stages of explant-induced reactivation, indicating that GR transcriptional activity has female-specific effects.
JOURNAL OF VIROLOGY
(2023)
Article
Microbiology
Harry H. Matundan, Ujjaldeep Jaggi, Jack Yu, Omid Akbari, Homayon Ghiasi
Summary: This study found that the interactions between CD28, CTLA4, and PD-L1 with CD80 can affect HSV-1 reactivation, leading to lower interferon signaling and reduced virus reactivation levels. Blocking these interactions could be a potential therapeutic target for HSV-1-induced reactivation and associated eye diseases.
Article
Virology
Michelle E. Wong, Chad J. Johnson, Anna C. Hearps, Anthony Jaworowski
Summary: In this study, a robust experimental model was established to quantify and investigate HIV reactivation in latently infected macrophages, showing that different macrophage phenotypes, cellular and tissue environments influence HIV reactivation. Additionally, the study demonstrated that certain latency-reversing agents may have different effects on latently infected macrophages compared to T cells, suggesting the need for dedicated strategies to target these populations in vivo.
JOURNAL OF VIROLOGY
(2021)
Article
Microbiology
Jesse H. Arbuckle, Jodi L. Vogel, Stacey Efstathiou, Thomas M. Kristie
Summary: Herpes simplex virus is a significant global disease burden. It establishes a lifelong persistent infection in sensory neurons. Transcription of the viral immediate early (IE) genes is regulated by the cellular transcriptional coactivator HCF-1, which is also involved in viral reactivation from latency. A study using an HCF-1 conditional knockout mouse model demonstrated that the deletion of HCF-1 in sensory neurons reduces the number of latently infected neurons that initiate viral reactivation. This is due to a defect in the removal of repressive chromatin associated with latent viral genomes. HCF-1 is therefore a critical regulatory factor for the initiation of HSV reactivation.
Article
Virology
Pankaj Singh, Matthew F. Collins, Richard N. Johns, Kayley A. Manuel, Ziyun A. Ye, David C. Bloom, Donna M. Neumann
Summary: This study revealed that during HSV-1 reactivation, the eviction of CTCF protein, especially from the CTRL2 insulator, may be necessary for efficient reactivation. Disruption of the CTRL2 insulator is essential for efficient HSV-1 reactivation. In the absence of CTRL2 insulator, HSV-1 can establish latent infection but fails to reactivate efficiently.
Article
Biochemistry & Molecular Biology
Jiradej Makjaroen, Pornpimol Phuengmaung, Wilasinee Saisorn, Suwasin Udomkarnjananun, Trairak Pisitkun, Asada Leelahavanichkul
Summary: Lipopolysaccharide (LPS) tolerance, which reduces the immune response to repeated LPS stimulation, may contribute to sepsis-induced immune exhaustion. Macrophages with LPS tolerance showed decreased energy, reduced protein abundance, and down-regulated anti-viral genes. In asymptomatic mice, LPS tolerance was associated with higher viral abundance in the cecum and decreased expression of anti-viral genes, suggesting it could lead to viral reactivation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Amanda L. Verzosa, Lea A. McGeever, Shun-Je Bhark, Tracie Delgado, Nicole Salazar, Erica L. Sanchez
Summary: This article discusses the transmission and lifecycle of alphaherpesviruses, with a focus on the impact of HSV-1 on host cell innate immune responses. It highlights how HSV-1 suppresses immune responses through various mechanisms, primarily in neuronal and epithelial cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Virology
Pankaj Singh, Donna M. Neumann
Summary: This study reveals that CTCF insulators in HSV-1 genomes are differentially enriched in the cohesin subunit Rad21, suggesting that CTCF-cohesin interactions are establishing and anchoring chromatin loop structures to control viral transcription.
JOURNAL OF VIROLOGY
(2021)
Article
Plant Sciences
Haitao Zhang, Jinfeng Cai, Chunna Li, Lisi Deng, Hongqiong Zhu, Ting Huang, Jiacong Zhao, Jiasheng Zhou, Kai Deng, Zhongsi Hong, Jinyu Xia
Summary: This study found that wogonin can suppress latent HIV-1 reactivation by inhibiting the expression of histone acetyltransferase p300 and decreasing the crotonylation of histone H3/H4 in the HIV-1 promoter region. This discovery holds promising significance for future applications in HIV-1 functional cure.
Article
Microbiology
Ariane Zutz, Lin Chen, Franziska Sippl, Andreas Humpe, Christian Schoelz
Summary: The study focused on screening latent reservoirs in HIV-1 infected individuals and identified two novel compounds with high reactivation efficiency and low toxicity as potential new treatment options for reversing latency.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Virology
Enrico R. Barrozo, Sanae Nakayama, Pankaj Singh, Donna M. Neumann, David C. Bloom
Summary: This study focuses on HSV-1 miRNA miR-H8 and its varying effects on viral yields and DNA replication during infection, demonstrating a minor role in HSV-1 latency or reactivation.
JOURNAL OF VIROLOGY
(2021)
Article
Ophthalmology
Kelly S. Harrison, Clinton Jones
Summary: Herpes simplex virus type 1 (HSV-1) can establish lifelong latency after infection, and the cycle of latency and reactivation is regulated by cellular stress and signaling pathways. Understanding these mechanisms is crucial for managing recurrent ocular disease.
EXPERIMENTAL EYE RESEARCH
(2022)
Article
Clinical Neurology
Angel Lin, Weam Othman Elbezanti, Alexis Schirling, Adel Ahmed, Rachel Van Duyne, Simon Cocklin, Zachary Klase
Summary: The HIV-1 pandemic poses a significant challenge to the field of medicine, with no cure yet found. Research has identified that the benzodiazepine Alprazolam could be an ideal candidate for latency reversal as it inhibits the transcription factor RUNX1 and increases STAT5 activation, potentially playing a positive role in addressing neuroinflammation associated with neuroHIV-1.
FRONTIERS IN NEUROLOGY
(2021)
Article
Virology
Emily Cruz-Lorenzo, Nora-Guadalupe P. Ramirez, Jeon Lee, Sonali Pandhe, Lei Wang, Juan Hernandez-Doria, Adam M. Spivak, Vicente Planelles, Tianna Petersen, Mamta K. Jain, Elisabeth D. Martinez, Ivan D'Orso
Summary: This study discovered a small molecule activator that alters the state of CD4(+) T cells to promote transcription and reactivation of latent HIV-1 through a unique mechanism of action. The activator triggered oxidative stress and activated a redox-responsive program involving cell-signaling kinases and atypical transcription factors, resulting in changes in viral transcriptional rewiring.
Review
Pharmacology & Pharmacy
Luis M. Schang, MiYao Hu, Esteban Flores Cortes, Kairui Sun
Summary: The ability of HSV-1 to establish, maintain and reactivate latent infections is regulated by epigenetics, which play a major role in these processes. The viral chromatin has distinct biophysical properties and is enriched in post translational modifications or histone variants that differ from cellular chromatin. Small molecule epigenetic modulators have shown to inhibit viral replication and reactivation from latency, suggesting potential for antiviral therapy.
ANTIVIRAL RESEARCH
(2021)