Article
Multidisciplinary Sciences
Ivana Yen, Frances Shanahan, Jeeyun Lee, Yong Sang Hong, Sang Joon Shin, Amanda R. Moore, Jawahar Sudhamsu, Matthew T. Chang, Inhwan Bae, Darlene Dela Cruz, Thomas Hunsaker, Christiaan Klijn, Nicholas P. D. Liau, Eva Lin, Scott E. Martin, Zora Modrusan, Robert Piskol, Ehud Segal, Avinashnarayan Venkatanarayan, Xin Ye, Jianping Yin, Liangxuan Zhang, Jin-Soo Kim, Hyeong-Seok Lim, Kyu-Pyo Kim, Yu Jung Kim, Hye Sook Han, Soo Jung Lee, Seung Tae Kim, Minkyu Jung, Yoon-hee Hong, Young Su Noh, Munjeong Choi, Oakpil Han, Malgorzata Nowicka, Shrividhya Srinivasan, Yibing Yan, Tae Won Kim, Shiva Malek
Summary: The study revealed that RAF dimer inhibitors may face resistance from melanoma cells with ARAF mutations, highlighting the potential of RAF plus MEK inhibition combination therapy to delay ARAF-driven resistance.
Article
Pharmacology & Pharmacy
Sunwen Chou, Matthew Watters, Rohita Sinha, Steven Kleiboeker
Summary: Research has found that mutations in the UL97 gene of cytomegalovirus, specifically in the ATP binding region, may impact the resistance to ganciclovir and maribavir. Therefore, it is suggested to include testing of the UL97 ATP binding region in the standard diagnostic genotyping for better interpretation of drug resistance.
ANTIVIRAL RESEARCH
(2021)
Article
Medicine, General & Internal
Mina Tasoujlu, Davod Khalafkhany, Khadijeh Makhdoomi, Morteza Motazakker
Summary: This study detected UL97 gene mutations associated with ganciclovir resistance in kidney transplant recipients, and identified two mutations related to resistance. Furthermore, a higher mutation rate of D605E was observed in the recipients.
BRATISLAVA MEDICAL JOURNAL-BRATISLAVSKE LEKARSKE LISTY
(2022)
Article
Microbiology
Xian-Zhang Wang, Le Wen, Yue-Peng Zhou, Sheng-Nan Huang, Bo Yang, Shuang Cheng, Wen-Bo Zeng, Meng-Jie Mei, Jin-Yan Sun, Xuan Jiang, Han Cheng, Min-Hua Luo
Summary: Congenital human cytomegalovirus (HCMV) infection leads to severe damage to the fetal brain. In this study, we discovered a new regulatory mechanism by which sustained SOCS3 expression is upregulated in HCMV-infected neural progenitor cells (NPCs). We found that the viral protein pUL97 interacts with and phosphorylates the host transcription factor RFX7, which drives the transcription of SOCS3. Elevated SOCS3 expression impairs NPC cell proliferation and migration, thereby affecting fetal brain development.
Article
Virology
Seungwan Chae, Hoon Seok Kim, Sung-Yeon Cho, Dukhee Nho, Raeseok Lee, Dong-Gun Lee, Myungshin Kim, Yonggoo Kim
Summary: This study aimed to identify variants associated with CMV drug resistance in HCT recipients and assess their clinical significance. The study found that 8.1% of patients had resistance variants, and 39.0% of patients had variants of uncertain significance. Patients with resistance variants had higher CMV viral load and higher risks of severe graft-versus-host disease and lower one-year survival rates.
Article
Pharmacology & Pharmacy
Steven B. Kleiboeker
Summary: Cytomegalovirus (CMV) is a significant human pathogen, with low but impactful prevalence of drug resistance mutations. In this study, 30.04% of patient samples showed resistance to one or more anti-CMV drugs, with most resistance mutations found in UL97. Rapid monitoring for resistance in suspected cases allows for tailored treatment based on objective results instead of empirical drug selection.
ANTIVIRAL RESEARCH
(2023)
Article
Virology
Vanessa Recio, Irene Gonzalez, David Tarrago
Summary: In a nationwide study, 26.87% of CMV positive transplant recipients had ARMs in UL97 and 10.60% had ARMs in UL54. The most prevalent ARMs were L595S/W and F412C, which conferred resistance to GCV and CDV. There was no significant difference in CMV load between patients with and without ARMs.
Article
Hematology
Fadi G. G. Haddad, Koji Sasaki, Aram Bidikian, Ghayas C. C. Issa, Tapan Kadia, Nitin Jain, Yesid Alvarado, Nicholas J. J. Short, Naveen Pemmaraju, Sanam Loghavi, Keyur P. P. Patel, Rashmi Kanagal-Shamanna, Musa Yilmaz, Lucia Masarova, Elias Jabbour, Hagop Kantarjian
Summary: Patients with chronic myeloid leukemia (CML) and T315I mutation have a poor prognosis. The survival of CML patients in the post-ponatinib era is uncertain. This study found that CML-CP patients at the time of T315I mutation detection had better survival compared to those in AP or BP. Treatment with third-generation tyrosine kinase inhibitors seemed to improve survival in CML-CP patients.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Avigail Stokar-Avihail, Taya Fedorenko, Jens Hor, Jeremy Garb, Azita Leavitt, Adi Millman, Gabriela Shulman, Nicole Wojtania, Sarah Melamed, Gil Amitai, Rotem Sorek
Summary: In recent years, various defense systems against phages have been found in bacteria. However, the mechanism of how these systems sense phage infection remains unknown. To address this question, the researchers isolated 177 phage mutants that can evade 15 different defense systems. These mutants were found to have mutations in the gene sensed by the defense system, providing insights into the determinants of phage sensitivity. The study identifies specific determinants of different retron systems and reveals phage-encoded triggers for abortive infection systems, shedding light on how bacterial immune systems sense phage invaders.
Article
Pharmacology & Pharmacy
G. Clement Dobbins, David W. Kimberlin, Shannon A. Ross
Summary: This study analyzed the variation of CMV in two patients with cCMV who received antiviral therapy. The results showed that there was an increase in CMV variation in the infant with a shorter treatment duration, while the infant with a longer treatment duration did not show an increase in CMV variation. This suggests that antiviral therapy may have an impact on CMV diversity.
ANTIVIRAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Zhanhong Liu, Pengbo Hou, Jiankai Fang, Jingyu Zhu, Juanmin Zha, Rui Liu, Yayun Ding, Muqiu Zuo, Peishan Li, Lijuan Cao, Chao Feng, Gerry Melino, Changshun Shao, Yufang Shi
Summary: Chemotherapy resistance in breast cancer can be induced by mesenchymal stromal cells (MSCs) through reducing the intratumoral accumulation of doxorubicin. This resistance is mediated by hyaluronan (HA), a major extracellular matrix (ECM) product of MSCs, which can bind with doxorubicin and inhibit its entry into breast cancer cells. High levels of HA in the serum are positively associated with chemoresistance in breast cancer patients.
Article
Microbiology
Han Chen, Ming F. Lye, Christoph Gorgulla, Scott B. Ficarro, Gregory D. Cuny, David A. Scott, Fan Wu, Paul W. Rothlauf, Xiaoou Wang, Rosio Fernandez, Jean M. Pesola, Sorin Draga, Jarrod A. Marto, James M. Hogle, Haribabu Arthanari, Donald M. Coen
Summary: The study found that two small molecule compounds, GK1 and GK2, selectively inhibit the replication of human cytomegalovirus (HCMV) by targeting the nuclear egress complex (NEC). These compounds could serve as a foundation for the development of anti-HCMV drugs and as chemical tools for studying HCMV.
Article
Multidisciplinary Sciences
Satoshi Tamura, Satoshi Osawa, Natsuki Ishida, Takahiro Miyazu, Shinya Tani, Mihoko Yamade, Moriya Iwaizumi, Yasushi Hamaya, Isao Kosugi, Takahisa Furuta, Ken Sugimoto
Summary: This study investigated the prevalence of CMV UL97 gene mutations in patients with colonic CMV infection associated with or without UC. The results showed that no known GCV resistance mutations were found in GCV-naive patients, regardless of the presence of UC. The D605E polymorphism may serve as a genetic marker for CMV in East Asian countries, consistent with previous reports.
SCIENTIFIC REPORTS
(2021)
Article
Genetics & Heredity
Karla Saavedra-Rodriguez, Corey L. Campbell, Saul Lozano, Patricia Penilla-Navarro, Alma Lopez-Solis, Francisco Solis-Santoyo, Americo D. Rodriguez, Rushika Perera, William C. Black
Summary: Pyrethroids are widely used to control the major vector of dengue, chikungunya, and Zika viruses, Ae. aegypti, but resistance mechanisms evolving in mosquito populations threaten disease control efforts. Two common resistance mechanisms involve knockdown resistance at the voltage-gated sodium channel and enhanced metabolism by detoxification enzymes. The proportions of different responses to pyrethroids are dependent on concentration and genetic background. This study identified genetic variants associated with resistance mechanisms in a pyrethroid-resistant colony from Tapachula, Mexico, providing insights into potential markers of resistance.
Article
Biochemistry & Molecular Biology
Keerthana Sasitharan, Hamzah Asad Iqbal, Foteini Bifsa, Aleksandra Olszewska, Kenneth J. Linton
Summary: The study investigates the role of hydrogen bonds and specific glutamines in drug recognition and transport by the ABCB1 efflux transporter. Results show that different glutamine mutations have varying effects on the transport of different drug classes, suggesting a complex mechanism of drug recognition. Surprisingly, some mutations improved drug transport, highlighting the intricate interactions within the drug binding pocket of ABCB1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)