RESUMEN
Background: Diagnosing the cause of headaches can be challenging. Even if intracranial lesions are found in a patient, careful assessment is essential for diagnosis, and treatment strategies will differ for each etiology. Case Description: A 16-year-old boy presented with sudden-onset headache which had lasted for 2 days. His headache was aggravated in the orthostatic position. The patient denied recent head trauma. He had been diagnosed with an arachnoid cyst (AC) in his right middle cranial fossa. Computed tomography (CT) revealed bilateral subdural effusions and slit-like lateral ventricles with no significant changes to the AC. After intravenous hydration followed by 2 days bed rest, his symptoms abated. He was diagnosed as having suffered spontaneous cerebrospinal fluid (CSF) hypovolemia. One month later, the patient experienced recurrent gradual onset headache and vomiting. CT revealed chronic right side subdural hematoma (SDH) with intracystic hemorrhage, which resulted in the elevation of intracranial pressure. An urgent hematoma evacuation was performed. He became symptom-free immediately after surgery. Postoperative follow-up CT showed no change in the AC and no recurrence of SDH. The lateral ventricles and subdural space were normal in size. Conclusion: We report a case presenting multiple types of secondary headaches, which were caused by intracranial hypotension or hypertension, with different etiologies. These were spontaneous CSF hypovolemia, nontraumatic intracystic hemorrhage form of AC, and nontraumatic chronic SDH. Although lesions seen at the time of initial diagnosis did not need surgical treatment, careful observation and repetitive imaging assessments might be useful for discovering unsuspected additional etiologies requiring surgical intervention.
RESUMEN
Endogenous retroviruses (ERVs) are sequences in animal genomes that originated from ancient retrovirus infections; they provide genetic novelty in hosts by being coopted as functional genes or elements during evolution. Recently, we demonstrated that endogenous elements from not only from retroviruses but also nonretroviral RNA viruses are a possible source of functional genes in host animals. The remnants of ancient bornavirus infections, called endogenous bornavirus-like elements (EBLs), are present in the genomes of a wide variety of vertebrate species, and some express functional products in host cells. Previous studies have predicted that the human EBL locus derived from bornavirus nucleoprotein, termed hsEBLN-2, expresses mRNA encoding a protein, suggesting that hsEBLN-2 has acquired a cellular function during evolution. However, the detailed function of the hsEBLN-2-derived product remains to be elucidated. In this study, we show that the hsEBLN-2-derived protein E2 acts as a mitochondrial protein that interacts with mitochondrial host factors associated with apoptosis, such as HAX-1. We also demonstrate that knockdown of hsEBLN-2-derived RNA increased the levels of PARP and caspase-3 cleavage and markedly decreased cell viability. In contrast, overexpression of E2 enhanced cell viability, as well as the intracellular stability of HAX-1, under stress conditions. Our results suggest that hsEBLN-2 has been coopted as a host gene, the product of which is involved in cell viability by interacting with mitochondrial proteins. IMPORTANCE Our genomes contain molecular fossils of ancient viruses, called endogenous virus elements (EVEs). Mounting evidence suggests that EVEs derived from nonretroviral RNA viruses have acquired functions in host cells during evolution. Previous studies have revealed that a locus encoding a bornavirus-derived EVE, hsEBLN-2, which was generated approximately 43 million years ago in a human ancestor, may be linked to the development of some tumors. However, the function of hsEBLN-2 has not been determined. In this study, we found that the E2 protein, an expression product of hsEBLN-2, interacts with apoptosis-related host proteins as a mitochondrial protein and affects cell viability. This study suggests that nonretroviral RNA viral EVEs have been coopted by hosts with more diverse functions than previously thought, showing a pivotal role for RNA virus infection in evolution.