In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
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Question: Among RNA viruses, the order Nidovirales stands out for including viruses with the largest RNA genomes currently known. Nidoviruses employ a complex RNAsynthesizing machinery comprising a variety of non-structural proteins (nsps). One of the postulated drivers of the expansion of nidovirus genomes is the presence of a proofreading 3 -to-5 exoribonuclease (ExoN) belonging to the DEDDh family. ExoN may enhance the fidelity of RNA synthesis by correcting nucleotide incorporation errors made by the RNA-dependent RNA polymerase. Here, we review our current understanding of ExoN evolution, structure, and function. Most experimental data are derived from studies of the ExoN domain of coronaviruses (CoVs), which were triggered by the bioinformatics-based identification of ExoN in the genome of severe acute respiratory syndrome coronavirus (SARS-CoV) and its relatives in 2003. Although convincing data supporting the proofreading hypothesis have been obtained, from biochemical assays and studies with CoV mutants lacking ExoN functionality, the features of ExoN from most other nidovirus families remain to be characterized. Remarkably, viable ExoN knockout mutants were obtained only for two CoVs, mouse hepatitis virus (MHV) and SARS-CoV, whose RNA synthesis and replication kinetics were mildly affected by the lack of ExoN function. In several other CoV species, ExoN inactivation was not tolerated, and knockout mutants could not be rescued when launched using a reverse genetics system. This suggests that ExoN is also critical for primary viral RNA synthesis, a property that poorly matches the profile of an enzyme that would merely boost longterm replication fidelity. In CoVs, ExoN resides in a bifunctional replicase subunit (nsp14) whose C-terminal part has (N7-guanine)-methyltransferase activity. The crystal structure of SARS-CoV nsp14 has shed light on the interplay between these two domains, and on nsp14's interactions with nsp10, a co-factor that strongly enhances ExoN activity in vitro assays. Further elucidation of the structure-function relationships of ExoN and its interactions with other (viral and/or host) members of the CoV replication machinery will be key to understanding the enzyme's role in viral RNA synthesis and pathogenesis, and may contribute to the design of new approaches to combat emerging nidoviruses.

Answer: The Curious Case of the Nidovirus Exoribonuclease: Its Role in RNA Synthesis and Replication Fidelity


Question: Human coronaviruses (HCoVs) are known respiratory pathogens associated with a range of respiratory outcomes. In the past 14 years, the onset of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) have thrust HCoVs into spotlight of the research community due to their high pathogenicity in humans. The study of HCoV-host interactions has contributed extensively to our understanding of HCoV pathogenesis. In this review, we discuss some of the recent findings of host cell factors that might be exploited by HCoVs to facilitate their own replication cycle. We also discuss various cellular processes, such as apoptosis, innate immunity, ER stress response, mitogen-activated protein kinase (MAPK) pathway and nuclear factor kappa B (NF-κB) pathway that may be modulated by HCoVs. Diseases 2016, 4, 26 2 of 28 but with a much higher mortality rate of about 35% [17] . Unlike SARS-CoV, which exhibits super-spreader events, transmission of MERS-CoV is geographically limited [12] . In fact, reported cases of MERS-CoV often stem from outbreaks within the Middle Eastern countries or recent travel to the region [18, 19] . CoVs are a group of large enveloped RNA viruses under the Coronaviridae family. Together with Artierivirdae and Roniviridae, Coronaviridae is classified under the Nidovirale order [20] . As proposed by the International Committee for Taxonomy of Viruses, CoVs are further categorized into four main genera, Alpha-, Beta-, Gammaand Deltacoronaviruses based on sequence comparisons of entire viral genomes [21, 22] . These CoVs can infect a wide variety of hosts, including avian, swine and humans. HCoVs are identified to be either in the Alphaor Betacoronavirus genera, including Alphacoronaviruses, HCoV-229E and HCoV-NL63, and Betacoronaviruses, HCoV-HKU1, SARS-CoV, MERS-CoV and HCoV-OC43 (Table 1) . Under the electron microscope, the CoV virions appear to be roughly spherical or moderately pleomorphic, with distinct "club-like" projections formed by the spike (S) protein [23, 24] . Within the virion interior lies a helically symmetrical nucleocapsid that encloses a single-stranded and positive sense RNA viral genome of an extraordinarily large size of about 26 to 32 kilobases [20] . The positive sense viral genomic RNA acts as a messenger RNA (mRNA), comprising a 5 1 terminal cap structure and a 3 1 poly A tail. This genomic RNA acts in three capacities during the viral life cycle: (1) as an initial RNA of the infectious cycle; (2) as a template for replication and transcription; and (3) as a substrate for packaging into the progeny virus. The replicase-transcriptase is the only protein translated from the genome, while the viral products of all downstream open reading frames are derived from subgenomic mRNAs. In all CoVs, the replicase gene makes up approximately 5 1 two-thirds of the genome and is comprised of two overlapping open reading frames (ORFs), ORF1a and ORF1b, which encodes 16 non-structural proteins. The final one-third of the CoV genomic RNA encodes CoV canonical set of four structural protein genes, in the order of spike (S), envelope (E), membrane (M) and nucleocapsid (N). In addition, several accessory ORFs are also interspersed along the structural protein genes and the number and location varies among CoV species [25] (Figure 1). Diseases 2016, 4, 26 2 of 27 SARS-CoV but with a much higher mortality rate of about 35% [17]. Unlike SARS-CoV, which exhibits super-spreader events, transmission of MERS-CoV is geographically limited [12]. In fact, reported cases of MERS-CoV often stem from outbreaks within the Middle Eastern countries or recent travel to the region [18,19]. CoVs are a group of large enveloped RNA viruses under the Coronaviridae family. Together with Artierivirdae and Roniviridae, Coronaviridae is classified under the Nidovirale order [20] . As proposed by the International Committee for Taxonomy of Viruses, CoVs are further categorized into four main genera, Alpha-, Beta-, Gamma-and Deltacoronaviruses based on sequence comparisons of entire viral genomes [21, 22] . These CoVs can infect a wide variety of hosts, including avian, swine and humans. HCoVs are identified to be either in the Alpha-or Betacoronavirus genera, including Alphacoronaviruses, HCoV-229E and HCoV-NL63, and Betacoronaviruses, HCoV-HKU1, SARS-CoV, MERS-CoV and HCoV-OC43 (Table 1) . Under the electron microscope, the CoV virions appear to be roughly spherical or moderately pleomorphic, with distinct "club-like" projections formed by the spike (S) protein [23, 24] . Within the virion interior lies a helically symmetrical nucleocapsid that encloses a single-stranded and positive sense RNA viral genome of an extraordinarily large size of about 26 to 32 kilobases [20] . The positive sense viral genomic RNA acts as a messenger RNA (mRNA), comprising a 5′ terminal cap structure and a 3′ poly A tail. This genomic RNA acts in three capacities during the viral life cycle: (1) as an initial RNA of the infectious cycle; (2) as a template for replication and transcription; and (3) as a substrate for packaging into the progeny virus. The replicase-transcriptase is the only protein translated from the genome, while the viral products of all downstream open reading frames are derived from subgenomic mRNAs. In all CoVs, the replicase gene makes up approximately 5′ twothirds of the genome and is comprised of two overlapping open reading frames (ORFs), ORF1a and ORF1b, which encodes 16 non-structural proteins. The final one-third of the CoV genomic RNA encodes CoV canonical set of four structural protein genes, in the order of spike (S), envelope (E), membrane (M) and nucleocapsid (N). In addition, several accessory ORFs are also interspersed along the structural protein genes and the number and location varies among CoV species [25] (Figure 1 ).

Answer: Human Coronaviruses: A Review of Virus-Host Interactions


Question: Humans are infected with many viruses, and the immune system mostly removes viruses and the infected cells. However, certain viruses have entered the human genome. Of the human genome, »45% is composed of transposable elements (long interspersed nuclear elements [LINEs], short interspersed nuclear elements [SINEs] and transposons) and 5-8% is derived from viral sequences with similarity to infectious retroviruses. If integration of retrovirus occurs in a germline, the integrated viral sequences are heritable. Accumulation of viral sequences has created the current human genome. This article summarizes recent studies of retroviruses in humans and bridges clinical fields and evolutionary genetics. First, we report the repertories of human-infective retroviruses. Second, we review endogenous retroviruses in the human genome and diseases associated with endogenous retroviruses. Third, we discuss the biological functions of endogenous retroviruses and propose the concept of accelerated human evolution via viruses. Finally, we present perspectives of virology in the field of evolutionary medicine.

Answer:
Evolutionary Medicine of Retroviruses in the Human Genome