Eukaryotic initiation factor 5A(eIF-5A) is a cellular cofactor require d for the function of the human immunodeficiency virus type-1 (HIV-1) Rev trans-activator protein. The majority of a set of eIF-5A mutants did not support growth of yeast cells having an inactivated genomic copy of eIF-5A, indicating that the introduced mutation eliminated eIF-5A activity. Two nonfunctional mutants, eIF-5AM13 and eIF-5AM14, retained their binding capacity for the HIV-1 Rev response element:Rev complex. Both mutants were constitutively expressed in human T cells. When these T cells were infected with replication-competent HIV-1, virus replication was inhibited. The eIF-5AM13 and eIF5AM14 proteins blocked Rev trans-activation and Rev-mediated nuclear export.
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http://dx.doi.org/10.1126/science.271.5257.1858 | DOI Listing |
Virology
December 2024
Section of Infectious Diseases, Department of Internal Medicine, Yale University, New Haven, CT, 06510, USA. Electronic address:
Significant advances in treatment have turned HIV-1 into a manageable chronic condition. This has been achieved due to highly active antiretroviral therapy (HAART), involving a combination regimen of medications, including drugs that target Reverse Transcriptase, Protease, Integrase, and viral entry, explored in this review. This paper also highlights novel therapies, such as Lenacapavir, and avenues toward functional cure targeting the CCR5 co-receptor, including the Δ32 mutation.
View Article and Find Full Text PDFNature
December 2024
Protein-Nucleic Acid Interaction Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
Much of the human genome is transcribed into RNAs, many of which contain structural elements that are important for their function. Such RNA molecules-including those that are structured and well-folded-are conformationally heterogeneous and flexible, which is a prerequisite for function, but this limits the applicability of methods such as NMR, crystallography and cryo-electron microscopy for structure elucidation. Moreover, owing to the lack of a large RNA structure database, and no clear correlation between sequence and structure, approaches such as AlphaFold for protein structure prediction do not apply to RNA.
View Article and Find Full Text PDFJCI Insight
December 2024
Graduate Program in Immunology, University of Michigan, Ann Arbor, United States of America.
Despite effective treatment, Human immunodeficiency virus (HIV) persists in optimally treated people as a transcriptionally silent provirus. Latently infected cells evade the immune system and the harmful effects of the virus, thereby creating a long-lasting reservoir of HIV. To gain a deeper insight into the molecular mechanisms of HIV latency establishment, we constructed a series of HIV-1 fluorescent reporter viruses that distinguish active versus latent infection.
View Article and Find Full Text PDFRev Med Inst Mex Seguro Soc
February 2024
Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas. Ciudad de México, México.
Curr Protoc
November 2024
Harvard Medical School, Microbiology Department, Boston, Massachusetts.
While various methods exist for examining and visualizing the structures of RNA molecules, dimethyl sulfate-mutational profiling and sequencing (DMS-MaPseq) stands out for its simplicity and versatility. This technique has been proven effective for studying RNA structures both in vitro and in complex biological settings. We present an updated protocol of DMS-MaPseq, as well as methodology that enables it to be used for detection of antisense oligonucleotides (ASOs) binding to RNA.
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