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Many viruses use a replication strategy involving the translation of a large polyprotein, which is cleaved by viral and/or cellular proteases. Several of these viruses severely impact human health around the globe, including HIV, HCV, Dengue virus, and West Nile virus. This method of genome organization has many benefits to the virus such as condensation of genetic material, as well as temporal and spatial regulation of protein activity depending on polyprotein cleavage state. The study of polyprotein precursors is necessary to fully understand viral infection, and identify possible new drug targets; however, few atomic structures are currently available. Presented here are structures of four recent polyprotein precursors from viruses with a positive sense RNA genome.
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http://dx.doi.org/10.1016/j.coviro.2013.03.009 | DOI Listing |
HIV-1 particle assembly depends critically on multiple proteolytic cleavages of viral polyproteins by the viral protease, PR. PR is translated as part of the Gag-Pro-Pol polyprotein, which undergoes autoproteolysis to liberate active, dimeric PR during virus particle maturation. Gag-Pro-Pol is produced via an infrequent -1 frameshifting event in ribosomes translating full length genomic RNA as Gag mRNA.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2025
Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.
Intracellular multivesicular bodies (MVBs) act as sites of assembly and release of HIV type 1 (HIV-1) in macrophages and microglia. Recent work has shown that processing of amyloid precursor protein (APP) into a C-terminal fragment (CTF), termed C99, inhibits HIV-1 access to CD63+ MVBs and to counteract this, HIV-1 Group-specific antigen (Gag) increases C99 processing into toxic amyloids. However, the underlying reasons for this negative interplay between Gag and C99 remain unclear.
View Article and Find Full Text PDFFront Bioinform
July 2025
Biological and Bio-computational Lab, Department of Life Science, Sharda School of Bio-Science and Technology, Sharda University, Greater Noida, Uttar Pradesh, India.
Introduction: Monkeypox is a serious viral illness that is rarely seen but is spread from person to person and from animals to humans. Cysteine proteinase, an essential enzyme involved in the replication of the monkeypox virus (MPXV), is one of many possible therapeutic targets for MPXV. The primary function of this enzyme is to cleave the precursor polyprotein into the distinct proteins required for viral assembly.
View Article and Find Full Text PDFPLoS One
April 2025
Department of Agricultural Convergence Technology, Jeonbuk National University, Jeonju, Republic of Korea.
The viral replication of foot-and-mouth disease virus (FMDV) and other picornaviruses primarily depends on the successful processing of a polyprotein precursor by the enzyme 3C protease (3Cpro) at specific sites. The crucial role of 3Cpro in viral replication and pathogenesis makes it a potential target for developing novel therapeutics against foot-and-mouth disease. The β-ribbon region (residues 138-150) containing the active site residues (C142) in 3Cpro is found to be conserved and contributes significantly to substrate specificity.
View Article and Find Full Text PDFVet Microbiol
May 2025
Division of Fundamental Immunology, National African Swine Fever Para-reference Laboratory, State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Harbin 150069, China; Heilongjiang Provincial Key Laborat
African Swine Fever (ASF) is a highly infectious viral disease caused by African swine fever virus (ASFV). Currently, there is no effective vaccine, and it is urgent to discover antiviral agents to deal with the epidemic. ASFV pS273R is the only known cysteine protease that catalyzes the maturation of the polyprotein precursors pp220 and pp62 through proteolytic cleavage, a critical step in ASFV assembly.
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