Article
Multidisciplinary Sciences
Alexandra B. Samal, Todd J. Green, Jamil S. Saad
Summary: This study reveals the detailed structure of the myrMA lattice and its role in Env incorporation during HIV-1 particle assembly. It was found that substitution of MA residues Leu13 and Leu31 induced a conformational change in myrMA, which may destabilize the trimer-trimer interactions within the lattice.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Virology
Maria Ines Barria, Raymond A. Alvarez, Kenneth Law, Deanna L. Wolfson, Thomas Huser, Benjamin K. Chen
Summary: The study examined the mechanism of simultaneous transfer of envelope protein and viral structural protein during HIV transmission, revealing a potential key role of endocytosed Env in optimizing productive infection in target cells.
Review
Microbiology
Connie Zhao, Hongru Li, Talia H. Swartz, Benjamin K. Chen
Summary: The HIV Env glycoprotein plays a crucial role in viral entry and antibody responses. Complex mechanisms allow HIV-1 Env to evade the immune system. Env on infected cells has distinct conformations compared to Env on virus particles. Understanding these differences is essential for vaccine design and therapeutic strategies.
Article
Virology
Lili Wang, Alice Sandmeyer, Wolfgang Huebner, Hongru Li, Thomas Huser, Benjamin K. Chen
Summary: HIV-1 infection is enhanced by cell-cell adhesions called virological synapses (VS), in which infected and uninfected T cells interact. This study used a replication-competent HIV-1 clone to track the movement of HIV-1 envelope glycoprotein (Env) within infected cells. The results showed that Env was dynamically exchanged at the VS, while the viral structural protein, Gag, remained immobile. Further experiments revealed that continuous internalization and targeted secretion were involved in the accumulation of Env at the VS and its incorporation into nascent particles.
Article
Microbiology
Silvia Perez-Yanes, Maria Pernas, Silvia Marfil, Romina Cabrera-Rodriguez, Raquel Ortiz, Victor Urrea, Carla Rovirosa, Judith Estevez-Herrera, Isabel Olivares, Concepcion Casado, Cecilio Lopez-Galindez, Julia Blanco, Agustin Valenzuela-Fernandez
Summary: The understanding of HIV-1 pathogenesis and clinical progression is incomplete due to the variable contribution of host, immune, and viral factors. This study analyzed the contribution of envelope glycoprotein complex (Env) from 41 specimens to different clinical progression rates and viral loads. The Envs from individuals with viral control showed lower performance and shorter sequences compared to progressors. Additionally, the variable loops of progressor Envs showed longer and more glycosylated sequences than those of controller subjects.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
James W. Bruce, Eunju Park, Chris Magnano, Mark Horswill, Alicia Richards, Gregory Potts, Alexander Hebert, Nafisah Islam, Joshua J. Coon, Anthony Gitter, Nathan Sherer, Paul Ahlquist
Summary: This study identified changes in protein levels and phosphorylation in HIV-1-infected cells after co-culture with CD4+ cells, with significant effects on cell cycle regulation. The cell cycle regulatory kinase AURKB was found to inhibit HIV-1 Env-mediated cell fusion and cell-to-cell transmission. The relocalization of AURKB to nuclear centrosomes induced by HIV-1 envelope-CD4 engagement prevented this suppression. These findings have important implications for understanding HIV-1 and cell processes, as well as potential therapeutic interventions.
Article
Virology
Grigoriy Lerner, Nicholas Weaver, Boris Anokhin, Paul Spearman
Summary: This review provides an overview of the HIV-1 assembly process, highlighting recent advances in the field and identifying areas for future investigation.
Review
Virology
Boris Anokhin, Paul Spearman
Summary: The HIV-1 envelope glycoprotein follows a unique pathway to reach the site of particle assembly, involving secretion, endocytosis, and directed sorting. The host factors and pathways regulating Env trafficking are still being explored. Understanding these processes is crucial for developing strategies to prevent viral infection and replication.
Article
Virology
Huxley K. Hoffman, Rebekah S. Aguilar, Austin R. Clark, Nicholas S. Groves, Nairi Pezeshkian, Merissa M. Bruns, Schuyler B. van Engelenburg
Summary: This study investigates the trafficking pathways of internalized HIV-1 envelope glycoprotein (Env) in infected CD4(+) T cells and the role of host cell Rab GTPases. The findings suggest that internalized Env traffics to Rab14(+) compartments that resemble late endosomes and lysosomes. Additionally, the study demonstrates that Env can be recycled back to the plasma membrane.
JOURNAL OF VIROLOGY
(2022)
Article
Neurosciences
Hyung Joon Cho, Martina Velichkovska, Nicolette Schurhoff, Ibolya E. Andras, Michal Toborek
Summary: This study investigated the mechanisms of HIV-1 infecting hNPCs and affecting NPC intercellular communications with HBMEC. It found that HIV-1 infection can alter connexin and pannexin channel communication in hNPCs and that EVs carrying A beta can modulate intercellular communications between infected hNPCs and HBMEC.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Multidisciplinary Sciences
Jeremie Prevost, Yaozong Chen, Fei Zhou, William D. Tolbert, Romain Gasser, Halima Medjahed, Manon Nayrac, Dung N. Nguyen, Suneetha Gottumukkala, Ann J. Hessell, Venigalla B. Rao, Edwin Pozharski, Rick K. Huang, Doreen Matthies, Andres Finzi, Marzena Pazgier
Summary: Resistance to the HIV-1 entry inhibitor temsavir is not solely determined by residue 375, but also involves other residues within the gp120 inner domain layers. The resistance is mediated by crosstalk between residue 375 and the inner domain layers. Additionally, temsavir has the ability to adjust its binding mode to accommodate changes in Env conformation, contributing to its broad antiviral activity.
NATURE COMMUNICATIONS
(2023)
Article
Virology
Neschika Jeewanraj, Tawanda Mandizvo, Takalani Mulaudzi, Nombali Gumede, Zaza Ndhlovu, Thumbi Ndung'u, Kamini Gounder, Jaclyn Mann
Summary: HIV-1 compartmentalisation may have significant implications for preventative vaccines and eradication strategies. Genetic analysis of HIV-1 subtype C variants in different compartments revealed partial viral compartmentalisation in most participants. The presence of neutralising antibody escape mutations in some individuals suggests that viral compartmentalisation should be considered in viral eradication efforts.
Article
Chemistry, Multidisciplinary
Chandan Kishor, Belinda L. Spillings, Johana Luhur, Corinne A. Lutomski, Chi-Hung Lin, William J. McKinstry, Christopher J. Day, Michael P. Jennings, Martin F. Jarrold, Johnson Mak
Summary: In this study, the authors use HIV as a model system to investigate the mechanism of directional protein delivery. They find that the viral assembly machinery Gag is copolarized with the intracellular calcium gradient and binds specifically with Ca2+. Mutation of Ca2+ binding amino acids affects protein trafficking and virion release.
Article
Biochemistry & Molecular Biology
Hussein Kaddour, Steven Kopcho, Yuan Lyu, Nadia Shouman, Victor Paromov, Siddharth Pratap, Chandravanu Dash, Eun-Young Kim, Jeremy Martinson, Heather McKay, Marta Epeldegui, Joseph B. Margolick, Jack T. Stapleton, Chioma M. Okeoma
Summary: This study shows how HIV infection and cocaine use affect the composition and function of semen-derived extracellular vesicles (EVs). The results reveal dysregulation of extracellular proteins and miRNAs in EVs, as well as changes in cell-cell interactions and monocyte movement. These findings provide insights into the potential impact of HIV infection and cocaine use on cellular processes.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Microbiology
Ntombikhona F. Maphumulo, Michelle L. Gordon
Summary: A study in Africa found that a subset of patients infected with HIV-1 subtype C experience virological failure on a second-line antiretroviral protease inhibitor treatment, and mutations in the Env gene may play a role in resistance to Lopinavir/Ritonavir. The study suggests that a combination of Env and Gag-PR mutations could contribute to potential pathways of resistance to LPV/r. Further investigations are needed to determine the impact of these mutations on viral fitness and the efficacy of LPV/r treatment.
MICROBIOLOGY RESEARCH
(2021)
Article
Virology
Kelly Watters, Bahar Inankur, Jaye C. Gardiner, Jay Warrick, Nathan M. Sherer, John Yin, Ann C. Palmenberg
JOURNAL OF VIROLOGY
(2017)
Article
Multidisciplinary Sciences
Cassie M. Jarvis, Daniel B. Zwick, Joseph C. Grim, Mohammad Murshid Alam, Lynne R. Prost, Jaye C. Gardiner, Soyeong Park, Laraine L. Zimdars, Nathan M. Sherer, Laura L. Kiessling
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Multidisciplinary Sciences
J. Alexander, D. B. Vendramini-Costa, R. Francescone, T. Luong, J. Franco-Barraza, N. Shah, J. C. Gardiner, E. Nicolas, K. S. Raghavan, E. Cukierman
Summary: Pancreatic Ductal Adenocarcinoma (PDAC) has a low five-year survival rate due to fibrotic stromal remodeling process driven by cancer-associated fibroblasts (CAFs). The study reveals that CAF activation and functions are closely related to the palladin iso3 and iso4 proteins, playing a crucial role in sustaining PDAC progression.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Kristopher S. Raghavan, Ralph Francescone, Janusz Franco-Barraza, Jaye C. Gardiner, Debora B. Vendramini-Costa, Tiffany Luong, Narges Pourmandi, Anthony Andren, Alison Kurimchak, Charline Ogier, Paul M. Campbell, James S. Duncan, Costas A. Lyssiotis, Lucia R. Languino, Edna Cukierman
Summary: It is projected that pancreatic cancer will become the second deadliest cancer in the United States in 5 years. Pancreatic ductal adenocarcinoma (PDAC) is characterized by a unique tumor microenvironment rich in cancer-associated fibroblasts (CAFs) and a dense extracellular matrix (ECM). These pathogenic CAF/ECM units lead to the collapse of local blood vessels, resulting in a nutrient-poor tumor microenvironment. PDAC cells are able to survive nutrient stress through support from CAF-secreted small extracellular vesicles (sEVs). The expression of NetrinG1 (NetG1) in CAFs and active Integrin ct5131 in multivesicular bodies are associated with poor patient survival. NetG1+ CAFs secrete sEVs that promote Akt-mediated survival in nutrient-deprived PDAC cells and protect them from apoptosis.
CANCER RESEARCH COMMUNICATIONS
(2022)