Multiple functions of heterogeneous nuclear ribonucleoproteins in the positive single-stranded RNA virus life cycle.

The heterogeneous nuclear ribonucleoproteins (hnRNPs) are a diverse family of RNA binding proteins that are implicated in RNA metabolism, such as alternative splicing, mRNA stabilization and translational regulation. According to their different cellular localization, hnRNPs display multiple functions. Most hnRNPs were predominantly located in the nucleus, but some of them could redistribute to the cytoplasm during virus infection. HnRNPs consist of different domains and motifs that enable these proteins to recognize predetermined nucleotide sequences. In the virus-host interactions, hnRNPs specifically bind to viral RNA or proteins. And some of the viral protein-hnRNP interactions require the viral RNA or other host factors as the intermediate. Through various mechanisms, hnRNPs could regulate viral translation, viral genome replication, the switch of translation to replication and virion release. This review highlights the common features and the distinguish roles of hnRNPs in the life cycle of positive single-stranded RNA viruses.

Functions of Viroporins in the Viral Life Cycle and Their Regulation of Host Cell Responses.

Viroporins are virally encoded transmembrane proteins that are essential for viral pathogenicity and can participate in various stages of the viral life cycle, thereby promoting viral proliferation. Viroporins have multifaceted effects on host cell biological functions, including altering cell membrane permeability, triggering inflammasome formation, inducing apoptosis and autophagy, and evading immune responses, thereby ensuring that the virus completes its life cycle. Viroporins are also virulence factors, and their complete or partial deletion often reduces virion release and reduces viral pathogenicity, highlighting the important role of these proteins in the viral life cycle. Thus, viroporins represent a common drug-protein target for inhibiting drugs and the development of antiviral therapies. This article reviews current studies on the functions of viroporins in the viral life cycle and their regulation of host cell responses, with the aim of improving the understanding of this growing family of viral proteins.

Tracing genetic signatures of bat-to-human coronaviruses and early transmission of North American SARS-CoV-2.

Highly pathogenic coronaviruses, including SARS-CoV-2, SARS-CoV and MERS-CoV, are thought to be transmitted from bats to humans, but the viral genetic signatures that contribute to bat-to-human transmission remain largely obscure. In this study, we identified an identical ribosomal frameshift motif among the three bat-human pairs of viruses and strong purifying selection after jumping from bats to humans. This represents genetic signatures of coronaviruses that are related to bat-to-human transmission. To further trace the early human-to-human transmission of SARS-CoV-2 in North America, a geographically stratified genome-wide association study (North American isolates and the remaining isolates) and a retrospective study were conducted. We determined that the single nucleotide polymorphisms (SNPs) 1,059.C > T and 25,563.G > T were significantly associated with approximately half of the North American SARS-CoV-2 isolates that accumulated largely during March 2020. Retrospectively tracing isolates with these two SNPs was used to reconstruct the early, reliable transmission history of North American SARS-CoV-2, and European isolates (February 26, 2020) showed transmission 3 days earlier than North American isolates and 17 days earlier than Asian isolates. Collectively, we identified the genetic signatures of the three pairs of coronaviruses and reconstructed an early transmission history of North American SARS-CoV-2. We envision that these genetic signatures are possibly diagnosable and predic markers for public health surveillance.