Recovery from Friend virus 3 (Rfv3) is a single autosomal gene encoding a resistance trait that influences retroviral neutralizing antibody responses and viremia. Despite extensive research for 30 years, the molecular identity of Rfv3 has remained elusive. Here, we demonstrate that Rfv3 is encoded by Apobec3. Apobec3 maps to the same chromosome region as Rfv3 and has broad inhibitory activity against retroviruses, including HIV. Not only did genetic inactivation of Apobec3 convert Rfv3-resistant mice to a susceptible phenotype, but Apobec3 was also found to be naturally disabled by aberrant messenger RNA splicing in Rfv3-susceptible strains. The link between Apobec3 and neutralizing antibody responses highlights an Apobec3-dependent mechanism of host protection that might extend to HIV and other human retroviral infections.
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http://dx.doi.org/10.1126/science.1161121 | DOI Listing |
Mol Syst Biol
January 2025
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, 76100, Israel.
Elevated cortisol in chronic stress and mood disorders causes morbidity including metabolic and cardiovascular diseases. There is therefore interest in developing drugs that lower cortisol by targeting its endocrine pathway, the hypothalamic-pituitary-adrenal (HPA) axis. However, several promising HPA-modulating drugs have failed to reduce long-term cortisol in mood disorders, despite effectiveness in other hypercortisolism conditions such as Cushing's syndrome.
View Article and Find Full Text PDFNat Microbiol
January 2025
KU Leuven Department of Microbiology, Immunology & Transplantation, Rega Institute, Laboratory of Molecular Vaccinology & Vaccine Discovery (MVVD), Leuven, Belgium.
J Invest Dermatol
January 2025
Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. Electronic address:
Contact hypersensitivity (CHS) and atopic dermatitis (AD) are pervasive inflammatory skin diseases with similar symptoms, and the global prevalence of both conditions is steadily rising. Many compounds and biotics have been developed to target molecules critical to the etiology or pathogenesis of CHS and AD. However, such molecules are sometimes ineffective or lose potency over the therapeutic course.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Biotechnology and Bioengineering, Sandia National Laboratories, Livermore, California, United States of America.
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to persist, demonstrating the risks posed by emerging infectious diseases to national security, public health, and the economy. Development of new vaccines and antibodies for emerging viral threats requires substantial resources and time, and traditional development platforms for vaccines and antibodies are often too slow to combat continuously evolving immunological escape variants, reducing their efficacy over time. Previously, we designed a next-generation synthetic humanized nanobody (Nb) phage display library and demonstrated that this library could be used to rapidly identify highly specific and potent neutralizing heavy chain-only antibodies (HCAbs) with prophylactic and therapeutic efficacy in vivo against the original SARS-CoV-2.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, Georgia, United States of America.
The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (β-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other β-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather than the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines.
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