Global mRNA Degradation during Lytic Gammaherpesvirus Infection Contributes to Establishment of Viral Latency

During a lytic gammaherpesvirus infection, host gene expression is severely restricted by the global degradation and altered 3′ end processing of mRNA. This host shutoff phenotype is orchestrated by the viral SOX protein, yet its functional significance to the viral lifecycle has not been elucidated, in part due to the multifunctional nature of SOX. Using an unbiased mutagenesis screen of the murine gammaherpesvirus 68 (MHV68) SOX homolog, we isolated a single amino acid point mutant that is selectively defective in host shutoff activity. Incorporation of this mutation into MHV68 yielded a virus with significantly reduced capacity for mRNA turnover. Unexpectedly, the MHV68 mutant showed little defect during the acute replication phase in the mouse lung. Instead, the virus exhibited attenuation at later stages of in vivo infections suggestive of defects in both trafficking and latency establishment. Specifically, mice intranasally infected with the host shutoff mutant accumulated to lower levels at 10 days post infection in the lymph nodes, failed to develop splenomegaly, and exhibited reduced viral DNA levels and a lower frequency of latently infected splenocytes. Decreased latency establishment was also observed upon infection via the intraperitoneal route. These results highlight for the first time the importance of global mRNA degradation during a gammaherpesvirus infection and link an exclusively lytic phenomenon with downstream latency establishment

Prophylactic Ilioinguinal Neurectomy in Open Inguinal Hernia Repair: A Double-Blind Randomized Controlled Trial

OBJECTIVE: We conducted a double-blinded randomized controlled trial to investigate the short- to mid-term neurosensory effect of prophylactic ilioinguinal neurectomy during Lichtenstein repair of inguinal hernia. METHOD: One hundred male patients between the age of 18 and 80 years with unilateral inguinal hernia undergoing Lichtenstein hernia repair were randomized to receive either prophylactic ilioinguinal neurectomy (group A) or ilioinguinal nerve preservation (group B) during operation. All operations were performed by surgeons specialized in hernia repair under local anesthesia or general anesthesia. The primary outcome was the incidence of chronic groin pain at 6 months. Secondary outcomes included incidence of groin numbness, postoperative sensory loss or change at the groin region, and quality of life measurement assessed by SF-36 questionnaire at 6 months. All follow-up and outcome measures were carried out by a designated occupational therapist at 1 and 6 months following surgery in a double-blinded manner. RESULTS: The incidence of chronic groin pain at 6 months was significantly lower in group A than group B (8% vs. 28.6%; P = 0.008). No significant intergroup differences were found regarding the incidence of groin numbness, postoperative sensory loss or changes at the groin region, and quality of life measurement at 6 months after the operation. CONCLUSIONS: Prophylactic ilioinguinal neurectomy significantly decreases the incidence of chronic groin pain after Lichtenstein hernia repair without added morbidities. It should be considered as a routine surgical step during the operation