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.

[EX Q]: Background: ISG15 is an Ubiquitin-like protein, highly induced by Type I Interferons. Upon the cooperative activity of specific Ubiquitinating enzymes, ISG15 can be conjugated to its substrates. Increasing evidence points to a role for protein ISGylation in anti-viral and anti-tumoral defense. Principal Findings: We identified ISG15 from Old World Monkeys (OWm) as a hyper-efficient protein modifier. Western blot analysis visualized more efficient conjugation of OWmISG15 relative to HuISG15 in human (Hu), monkey and mouse (Mo) cell-lines. Moreover, the substrates of OWmISG15 identified upon Tandem Affinity Purification followed by LC-MS/MS identification largely outnumbered these of HuISG15 itself. Several Ubiquitin-Conjugating enzymes were identified as novel ISGylated substrates. Introduction of a N89D mutation in HuISG15 improved its ISGylation capacity, and additional Q31K/ T33A/D133N mutations yielded a HuISG15 variant with an ISGylation efficiency comparable to OWmISG15. Homology modeling and structural superposition situate N89 in the interaction interface with the Activating enzyme. Analysis of the UbE1L residues in this interface revealed a striking homology between OWmUbE1L and HuUbE1, the Activating enzyme of Ubiquitin. In line with this observation, we found efficient activation of AgmISG15, but not HuISG15 or MoISG15, by HuUbE1, thus providing a likely explanation for OWm hyperISGylation. Conclusions: This study discloses the poor conjugation competence of HuISG15 compared to OWmISG15 and maps the critical determinants for efficient conjugation. HyperISGylation may greatly assist ISGylation studies and may enhance its function as positive regulator of Interferon-related immune responses or as anti-tumoral modulator.
[EX A]: HyperISGylation of Old World Monkey ISG15 in Human Cells

[EX Q]: Attenuated viral vaccines can be generated by targeting essential pathogenicity factors. We report here the rational design of an attenuated recombinant coronavirus vaccine based on a deletion in the coding sequence of the nonstructural protein 1 (nsp1). In cell culture, nsp1 of mouse hepatitis virus (MHV), like its SARS-coronavirus homolog, strongly reduced cellular gene expression. The effect of nsp1 on MHV replication in vitro and in vivo was analyzed using a recombinant MHV encoding a deletion in the nsp1-coding sequence. The recombinant MHV nsp1 mutant grew normally in tissue culture, but was severely attenuated in vivo. Replication and spread of the nsp1 mutant virus was restored almost to wild-type levels in type I interferon (IFN) receptor-deficient mice, indicating that nsp1 interferes efficiently with the type I IFN system. Importantly, replication of nsp1 mutant virus in professional antigen-presenting cells such as conventional dendritic cells and macrophages, and induction of type I IFN in plasmacytoid dendritic cells, was not impaired. Furthermore, even low doses of nsp1 mutant MHV elicited potent cytotoxic T cell responses and protected mice against homologous and heterologous virus challenge. Taken together, the presented attenuation strategy provides a paradigm for the development of highly efficient coronavirus vaccines.
[EX A]: Coronavirus Non-Structural Protein 1 Is a Major Pathogenicity Factor: Implications for the Rational Design of Coronavirus Vaccines

[EX Q]: The human metapneumovirus (hMPV) is a newly described member of the Paramyxoviridae family belonging to the Metapneumovirus genus. Since its initial description in 2001, hMPV has been reported in most parts of the world and isolated from the respiratory tract of subjects from all age groups. Despite the fact that prospective and case-control studies have been limited, the epidemiology and clinical manifestations associated with hMPV have been found to be reminiscent of those of the human respiratory syncytial virus, with most severe respiratory tract infections occurring in infants, elderly subjects, and immunocompromised hosts. Additional research is needed to define the pathogenesis of this viral infection and the host's specific immune response. Acute respiratory tract infections (ARTIs) are a major cause of morbidity and mortality worldwide. A variety of viruses, including the influenza viruses, human respiratory syncytial virus (hRSV), parainfluenza viruses, adenoviruses, rhinoviruses, and coronaviruses, have been associated with clinical syndromes ranging from mild illnesses, such as the common cold, to more severe devastating conditions, such as pneumonia. However, ∼50% of the cases of community-acquired pneumonia in adults and 15%-35% of cases of bronchiolitis and pneumonia in pediatric patients are still without a known etiology [1-3]. Along with inadequate diagnostic methods, this observation also suggests that other respiratory tract infectious agents may exist and remain to be identified. A new respiratory virus, the human metapneumovirus (hMPV) was first isolated in 2001 from nasopharyngeal aspirates (NPAs) obtained from young children in The Netherlands [4] . On the basis of morphological, biochemical, and genetic features, hMPV was tentatively classified with avian metapneumovirus (APV), the causative agent of an upper respiratory tract disease in turkeys and other birds [5], in the Metapneumovirus genus. The latter, together with the Pneumovirus genus (containing hRSV as the type species), is Note added in proof. Human metapneumovirus was recently isolated from previously virus-negative nasal wash specimens from 49 (20%) of 248 young children consulting at the Vanderbilt Clinic (Nashville, TN) for lower respiratory tract illnesses [44] . Extrapolation of these results to the entire cohort of patients observed at this institution over a 25-year period (1976-2001) suggests that the prevalence of human metapneumovirus infection was ∼12% in all outpatient children with lower respiratory tract diseases.
[EX A]:
Human Metapneumovirus: A New Player among Respiratory Viruses