Molecular Determinants of Flavivirus Virion Assembly

Viral RNAs contain the information needed to synthesize their own proteins, to replicate, and to spread to susceptible cells. However, due to their reduced coding capacity RNA viruses rely on host cells to complete their multiplication cycle. This is largely achieved by the concerted action of regulatory structural elements on viral RNAs and a subset of host proteins, whose dedicated function across all stages of the infection steps is critical to complete the viral cycle. Importantly, not only the RNA sequence but also the RNA architecture imposed by the presence of specific structural domains mediates the interaction with host RNA-binding proteins (RBPs), ultimately affecting virus multiplication and spreading. In marked difference with other biological systems, the genome of positive strand RNA viruses is also the mRNA. Here we focus on distinct types of positive strand RNA viruses that differ in the regulatory elements used to promote translation of the viral RNA, as well as in the mechanisms used to evade the series of events connected to antiviral response, including translation shutoff induced in infected cells, assembly of stress granules, and trafficking stress.

Section: Discussionmentioning

confidence: 99%

RNA-Binding Proteins at the Host-Pathogen Interface Targeting Viral Regulatory Elements

Embarc-Buh

Francisco‐Velilla

Martínez-Salas

2021

“…However, the trans-complementary assay only recovers virion production activity and not RNA replication, suggesting that two different sets of NS2A at different cellular locations are involved in each process [ 65 , 67 ]. The role of NS2A in the virus assembly process was recently reviewed by Barnard et al, 2021 [ 68 ]. However, more studies are required to fully understand the role of NS2A in viral RNA replication.…”

Section: Nonstructural Proteinsmentioning

confidence: 99%

Molecular Insights into the Flavivirus Replication Complex

Elsen

Quek

Luo

2021

Flaviviruses are vector-borne RNA viruses, many of which are clinically relevant human viral pathogens, such as dengue, Zika, Japanese encephalitis, West Nile and yellow fever viruses. Millions of people are infected with these viruses around the world each year. Vaccines are only available for some members of this large virus family, and there are no effective antiviral drugs to treat flavivirus infections. The unmet need for vaccines and therapies against these flaviviral infections drives research towards a better understanding of the epidemiology, biology and immunology of flaviviruses. In this review, we discuss the basic biology of the flavivirus replication process and focus on the molecular aspects of viral genome replication. Within the virus-induced intracellular membranous compartments, flaviviral RNA genome replication takes place, starting from viral poly protein expression and processing to the assembly of the virus RNA replication complex, followed by the delivery of the progeny viral RNA to the viral particle assembly sites. We attempt to update the latest understanding of the key molecular events during this process and highlight knowledge gaps for future studies.

“…While the structural proteins become physical components of the new viral progeny, many of the nonstructural proteins play crucial roles in facilitating viral replication, in part, by manipulating the ER structure [ 68 ]. These manipulations produce different ER-derived structures that in turn support replication of the viral genome ( Figure 3 , step 4) [ 68 , 69 ].…”

Section: Hijacking Cytosolic and Er-localized Chaperones To Promote Flavivirus Infectionmentioning

confidence: 99%

“…This is initiated when the viral genomic RNA and C protein merge to become the nucleocapsid—the nucleocapsid then buds into the ER lumen at an assembly site, recruiting the prM and E membrane proteins in the process. The assembled immature viral particle subsequently leaves the ER via an exit site, trafficking to the Golgi where it undergoes further maturation ( Figure 3 , step 6) [ 69 , 70 ]. Finally, the mature virus exits the host cell via transport along the anterograde pathway en route for secretion ( Figure 3 , step 7).…”

Section: Hijacking Cytosolic and Er-localized Chaperones To Promote Flavivirus Infectionmentioning

confidence: 99%

How DNA and RNA Viruses Exploit Host Chaperones to Promote Infection

Speckhart

Williams

Tsai

2021

To initiate infection, a virus enters a host cell typically via receptor-dependent endocytosis. It then penetrates a subcellular membrane, reaching a destination that supports transcription, translation, and replication of the viral genome. These steps lead to assembly and morphogenesis of the new viral progeny. The mature virus finally exits the host cell to begin the next infection cycle. Strikingly, viruses hijack host molecular chaperones to accomplish these distinct entry steps. Here we highlight how DNA viruses, including polyomavirus and the human papillomavirus, exploit soluble and membrane-associated chaperones to enter a cell, penetrating and escaping an intracellular membrane en route for infection. We also describe the mechanism by which RNA viruses—including flavivirus and coronavirus—co-opt cytosolic and organelle-selective chaperones to promote viral endocytosis, protein biosynthesis, replication, and assembly. These examples underscore the importance of host chaperones during virus infection, potentially revealing novel antiviral strategies to combat virus-induced diseases.