Murine Retrovirus Escapes from Murine APOBEC3 via Two Distinct Novel Mechanisms

SummaryAPOBEC3G (A3G) is an antiretroviral host factor that functions by deaminating dC to dU in retroviral cDNA [1–5]. HIV-1 Vif protein counteracts A3G via a ubiquitin-proteasome pathway [6–12]. In the case of a simple retrovirus such as the murine leukemia virus (MLV), it remains unclear why it can replicate in cells expressing APOBEC3 (A3) even though it doesn't possess any accessory proteins such as Vif [2, 13]. In this study, we demonstrate that MLV escapes from murine A3 (mA3) via two distinct novel mechanisms. First, viral RNA (vRNA) blocks the binding of mA3 to Gag, resulting in the exclusion of mA3 from MLV virions. Second, viral protease (vPR) cleaves mA3 after maturation of virions. Here, we suggest that each virus has its own strategy to escape from A3 proteins and that these mechanisms might be used by other viruses that do not possess Vif-like protein. On the other hand, mice possess another form of mA3, Δexon5, that escapes from the cleavage by vPR to show more antiviral activity than the wild type mA3. This also suggests that battles between host intrinsic immunity and viruses have led to the evolution of proteins on both sides

APOBEC3G targets human T-cell leukemia virus type 1

BACKGROUND: Apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) is a host cellular protein with a broad antiviral activity. It inhibits infectivitiy of a wide variety of retroviruses by deaminating deoxycytidine (dC) into deoxyuridine (dU) in newly synthesized minus strand DNA, resulting in G-to-A hypermutation of the viral plus strand DNA. To clarify the mechanism of its function, we have examined the antiviral activity of APOBEC3G on human T-cell leukemia virus type 1 (HTLV-1), the first identified human retrovirus. RESULTS: In this study, we have demonstrated that overexpressed as well as endogenous APOBEC3G were incorporated into HTLV-1 virions and that APOBEC3G inhibited the infection of HTLV-1. Interestingly, several inactive mutants of APOBEC3G also inhibited HTLV-1 and no G-to-A hypermutation was induced by APOBEC3G in HTLV-1 genome. Furthermore, we introduced the human immunodeficiency virus type 1 (HIV-1) vif gene into HTLV-1 producing cell line, MT-2, to antagonize APOBEC3G by reducing its intracellular expression and virion incorporation, which resulted in upregulation of the infectivity of produced viruses. CONCLUSION: APOBEC3G is incorporated into HTLV-1 virions and inhibits the infection of HTLV-1 without exerting its cytidine deaminase activity. These results suggest that APOBEC3G might act on HTLV-1 through different mechanisms from that on HIV-1 and contribute to the unique features of HTLV-1 infection and transmission

Results of laparoscopic subtotal cholecystectomy by laparoscopic linear stapler in difficult cases with severe cholecystitis

Laparoscopic subtotal cholecystectomy (LSC) has been recognized as a safe and feasible alternative surgical procedure for a difficult laparoscopic cholecystectomy (LC) with severe inflammation in Calot’s triangle. We compared the surgical outcomesof cholecystectomy for acute cholecystitis between standard LC and LSC using laparoscopic linear stapler. 172 patients were diagnosed as acute cholecystitis, among them, 16 patients who underwent LSC and other 156 patients who underwent standardLC were enrolled in this study. The severity grading of acute cholecystitis in LSC group was significantly higher than LC group. Operation time was longer in the LSC group than LC group. LSC had significantly more intraoperative blood loss compared to LC. However, there was no significant difference in the postoperative complications between two groups. LSC using laparoscopic linear stapler contributes surgeons avoid common bile duct injury in difficult LC

A case of surgical resection for well-differentiated squamous cell carcinoma arising in a ciliated hepatic foregut cyst

Ciliated hepatic foregut cysts (CHFC) are extremely rare, and most are benign cysts of the liver arising from remnants of the embryonic foregut. CHFC is usually found incidentally and as mostly asymptomatic cysts. We report squamous cell carcinoma (SCC) arising in a CHFC in a 50-year-old Japanese woman. She consulted our hospital for upper abdominal pain.A computed tomography and an ultrasound showed a cystic region including calcification and a solid mass in segment 4 of the liver. Left hepatectomy, B6 bile duct resection, and biliary-jejunal anastomosis were performed. Microscopic examination revealed that part of the cyst was lined by a characteristic ciliated pseudostratified columnar epithelium surrounding a connective tissue, a slightly thick fibrotic smooth muscle stromal layer, and an outer fibrous capsule. The cyst wall contained a low-papillary mural nodule showing atypical squamous hyperplasia with high-grade dysplasia. Stromal invasion was identified at the base of the nodule, leading to the diagnosis of well-differentiated SCC arising from a CHFC. We recommend careful clinical follow-up for patients with relatively large CHFCs as potentially malignant lesions and excision if they show any clinical manifestation