The carboxy terminus-encoding portion of the gag gene of Mason-Pfizer monkey virus (M-PMV), the prototype immunosuppressive primate type D retrovirus, encodes a 36-amino-acid, proline-rich protein domain that, in the mature virion, becomes the p4 capsid protein. The p4 domain has no known role in M-PMV replication. We found that two mutants with premature termination codons that remove half or all of the p4 domain produced lower levels of stable Gag protein and of self-assembled capsids. Interestingly, yeast twohybrid screening revealed that p4 specifically interacted with TCP-1␥, a subunit of the chaperonin TRiC (TCP-1 ring complex). TRiC is a cytosolic chaperonin that is known to be involved in both folding and subunit assembly of a variety of cellular proteins. TCP-1␥ also associated with high specificity with the M-PMV pp24/16-p12 domain and human immunodeficiency virus p6. Moreover, in cells, Gag polyprotein associated with the TRiC chaperonin complex and this association depended on ATP hydrolysis. In the p4 truncation mutants, the Gag-TRiC association was significantly reduced. These results strongly suggest that cytosolic chaperonin TRiC is involved in Gag folding and/or capsid assembly. We propose that TRiC associates transiently with nascent M-PMV Gag molecules to assist in their folding. Consequently, properly folded Gag molecules carry out the intermolecular interactions involved in self-assembly of the immature capsid.

Retroviral capsid assembly can occur by either of two distinct morphogenic processes: in type C viruses, the capsid assembles and buds at the plasma membrane, while in type B and D viruses, the capsid assembles within the cytoplasm and is then transported to the plasma membrane for budding. We have previously reported that a single-amino-acid substitution of a tryptophan for an arginine in the matrix protein (MA) of Mason-Pfizer monkey virus (MPMV) converts its capsid assembly from that of a type D retrovirus to that of the type C viruses (S. S. Rhee and E. Hunter, Cell 63:77–86, 1990). Here we identify a region of 18 amino acids within the MA of MPMV that is responsible for type D-specific morphogenesis. Insertion of these 18 amino acids into the MA of type C Moloney murine leukemia virus causes it to assemble an immature capsid in the cytoplasm. Furthermore, fusion of the MPMV MA to the green fluorescent protein resulted in altered intracellular targeting and a punctate accumulation of the fusion protein in the cytoplasm. These 18 amino acids, which are necessary and sufficient to target retroviral Gag polyproteins to defined sites in the cytoplasm, appear to define a novel mammalian cytoplasmic targeting/retention signal.

BACKGROUND Primary hepatic sarcoma is a rare tumor originated from mesenchymal tissue. There are various pathologic types of primary hepatic sarcoma and the treatment outcome of this tumor was usually disappointing. Unlike hepatocellular carcinoma, outcome of primary hepatic sarcoma is not well-known due to it’s rarity. However, with development of medical technology, surgical treatment may lead to better survival. AIM To investigate the surgical outcomes of primary hepatic sarcoma, we gathered and analyzed the cases of a single institute. METHODS From August 2001 to September 2016, a total of nine patients were surgically treated for primary hepatic sarcoma after exclusion of cases with open and closure, early loss to follow-up and sarcomatoid hepatocellular carcinoma and sarcomatoid cholangiocellular carcinoma. Baseline characteristics, tumor characteristics such as tumor pathology, size and number, surgical and adjuvant treatments were reviewed. Tumor recurrence, and patient survival were analyzed with retrospective approach. RESULTS The enrolled participants included five patients with angiosarcoma and four patients with undifferentiated sarcoma. All patients experienced tumor recurrence at a median of 52 post-operative days. Only two patients survived and the 5-year survival rate was 29.6%. One patient with angiosarcoma who received central hepatectomy for primary tumor and received radiofrequency ablation for recurrent tumor still lives for 11 years. One patient with undifferentiated sarcoma received Rt. lobectomy for primary tumor followed by chemotherapy and radiation therapy still lives around 30 mo even though she got additional operation for recurrent tumor. Two patients who received living donor liver transplantation due to angiosarcoma died. Only adjuvant therapy was associated with survival gain ( P = 0.002). CONCLUSION Patients with primary hepatic sarcoma may gain survival benefit with surgical resection followed by adjuvant therapy, even though the outcome remains relatively poor.

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