Human coronaviruses (CoVs) such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV) cause epidemics of severe human respiratory disease. A conserved step of CoV replication is the translation and processing of replicase polyproteins containing 16 nonstructural protein domains (nsp's 1 to 16). The CoV nsp5 protease (3CLpro; Mpro) processes nsp's at 11 cleavage sites and is essential for virus replication. CoV nsp5 has a conserved 3-domain structure and catalytic residues. However, the intra-and intermolecular determinants of nsp5 activity and their conservation across divergent CoVs are unknown, in part due to challenges in cultivating many human and zoonotic CoVs. To test for conservation of nsp5 structure-function determinants, we engineered chimeric betacoronavirus murine hepatitis virus (MHV) genomes encoding nsp5 proteases of human and bat alphacoronaviruses and betacoronaviruses. Exchange of nsp5 proteases from HCoV-HKU1 and HCoV-OC43, which share the same genogroup, genogroup 2a, with MHV, allowed for immediate viral recovery with efficient replication albeit with impaired fitness in direct competition with wild-type MHV. Introduction of MHV nsp5 temperature-sensitive mutations into chimeric HKU1 and OC43 nsp5 proteases resulted in clear differences in viability and temperature-sensitive phenotypes compared with MHV nsp5. These data indicate tight genetic linkage and coevolution between nsp5 protease and the genomic background and identify differences in intramolecular networks regulating nsp5 function. Our results also provide evidence that chimeric viruses within coronavirus genogroups can be used to test nsp5 determinants of function and inhibition in common isogenic backgrounds and cell types. C oronaviruses (CoVs) are enveloped, positive-strand RNA viruses that infect a wide range of animal hosts. Human CoVs cause illnesses including the common cold and severe acute respiratory syndrome (SARS) as well as the recently identified Middle East respiratory syndrome (MERS) associated with infection of a novel coronavirus (1). Coronaviruses are members of the order Nidovirales, family Coronaviridae, and subfamily Coronavirinae. Among the viruses in Coronavirinae, four main genera have recently been designated (2): alphacoronaviruses, which contain human coronavirus 229E (HCoV-229E) and HCoV-NL63; betacoronaviruses, containing human coronaviruses SARS-CoV, HKU1, MERS-CoV, and OC43; and gammacoronaviruses and deltacoronaviruses, from which no current human coronaviruses have been identified. The betacoronavirus murine hepatitis virus (MHV) is a well-established model for the study of coronavirus replication and pathogenesis. The MHV genome is 32 kb in length and encodes 7 genes (Fig. 1A) (3-5). An essential step of CoV replication is the translation of the ORF1ab replicase polyproteins and the subsequent processing of up to 16 nonstructural proteins (nsp's 1 to 16), including the nsp12 RNA-dependent RNA polymerase (3,5,6). CoV nsp5 protease (3CLpro; Mpro) med...

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Tumors of the testes are the most common solid organ malignancy in young men. The first modality of choice for intratesticular masses is high-resolution sonography. The majority of intratesticular masses are malignant and ultrasound (US) remains the first-line modality for evaluation of these masses. While rare, benign testicular masses are important to recognize to avoid unnecessary workup and surgery. We present the case of a 38-year-old male with a testicular hemangioma, a rare benign testicular tumor. US and pathologic findings of this tumor are discussed.

Intractable or drug-resistant seizures in pediatric patients are often secondary to cortical malformations, hamartomas, or mass lesions. Various subtypes of intracerebral hamartomas, associated with seizure disorders, have been described. In this report, we describe a subtype of intracerebral hamartoma associated with intractable epilepsy in a 10-year-old patient. Initial MR imaging demonstrated a mildly expansile, T2/FLAIR hyperintense, T1 isointense, nonenhancing lesion with blurring of the gray-white junction in the left amygdala. Surgical resection was performed, and pathology confirmed oligodendroglial hamartoma. Patient’s seizures recurred after a two-year interval with imaging demonstrating a similar lesion in the right amygdala which in retrospect was also seen on multiple imaging studies. This case report demonstrates the importance of recognizing oligodendroglial hamartomas as a cause of intractable seizures given the imaging findings, distinguishing it from ganglioglioma, dysembryoplastic neuroepithelial tumor, and oligodendroglioma, and the importance of closely looking/searching for contralateral lesions, which has important therapeutic and prognostic implications.