HTLV-1 structural proteins.

HTLV-1 structural proteins do not appear to ensure virus transmission as efficiently as most other retrovirus structural proteins do, whereas all other retroviruses can be transmitted via either free virions or cell-to-cell contacts, infection by HTLV-1 by free virions is very inefficient, and effective infection requires the presence of HTLV-1 infected cells. This characteristic feature of HTLV-1 provides a unique tool which can be used to analyse retrovirus cellular transmission in the absence of simultaneous cell-free infection. Here we summarise what is known about HTLV-1 structural proteins and identify the questions about these proteins which remain to be answered.

Zenker's diverticulum associated with multilevel cervical osteomyelitis.

STUDY DESIGN: A case report of cervical osteomyelitis possibly associated with a Zenker's diverticulum perforation. OBJECTIVES: To present clinical, radiologic, and surgical findings of a cervical osteomyelitis due to a Zenker's diverticulum perforation. SUMMARY OF BACKGROUND DATA: A 56-year-old patient was in an intensive care unit for a severe head injury. He was fed via a nasogastric tube. Four months later he developed a pyogenic cervical vertebral infection. METHODS: Plain films and magnetic resonance imaging showed a diffuse cervical osteomyelitis. Investigation of his dysphagia revealed a Zenker's diverticulum. RESULTS: After administration of antibiotics and surgical treatment of the diverticulum, the cervical infection resolved. Plain films and magnetic resonance imaging showed healing with vertebral fusion. CONCLUSIONS: Cervical osteomyelitis is uncommon. Only one case of direct contamination leading to cervical vertebral osteomyelitis after esophageal perforation has been previously described. Direct contamination of the prevertebral soft tissues by bacteria traveling through the fistula may have occurred. The development of vertebral osteomyelitis in this case is consistent with the hypothesis of direct contamination. Management relies on appropriate antimicrobial therapy and surgical management of the diverticulum. The association of Zenker's diverticulum with vertebral osteomyelitis and discitis is a unique, previously undescribed situation.

Identification of two intracellular mechanisms leading to reduced expression of oncoretrovirus envelope glycoproteins at the cell surface.

All retrovirus glycoproteins have a cytoplasmic domain that plays several roles in virus replication. We have determined whether and how the cytoplasmic domains of oncoretrovirus glycoproteins modulate their intracellular trafficking, by using chimeric proteins that combined the alpha-chain of the interleukin-2 receptor with the glycoprotein cytoplasmic domains of five oncoretroviruses: human T-cell leukemia virus type 1 (HTLV-1), Rous sarcoma virus (RSV), bovine leukemia virus (BLV), murine leukemia virus (MuLV), and Mason-Pfizer monkey virus (MPMV). All of these proteins were synthesized and matured in the same way as a control protein with no retrovirus cytoplasmic domain. However, the amounts of all chimeric proteins at the cell surface were smaller than that of the control protein. The protein appearing at and leaving the cell surface and endocytosis were measured in stable transfectants expressing the chimera. We identified two groups of proteins which followed distinct intracellular pathways. Group 1 included chimeric proteins that reached the cell surface normally but were rapidly endocytosed afterwards. This group included the chimeric proteins with HTLV-1, RSV, and BLV cytoplasmic domains. Group 2 included chimeric proteins that were not detected at the cell surface, despite normal intracellular concentrations, and were accumulated in the Golgi complex. This group included the chimeric proteins with MuLV and MPMV cytoplasmic domains. Finally, we verified that the MuLV envelope glycoproteins behaved in the same way as the corresponding chimeras. These results indicate that retroviruses have evolved two distinct mechanisms to ensure a similar biological feature: low concentrations of their glycoproteins at the cell surface.

The Y-S-L-I tyrosine-based motif in the cytoplasmic domain of the human T-cell leukemia virus type 1 envelope is essential for cell-to-cell transmission.

The human T-cell leukemia virus type 1 (HTLV-1) transmembrane glycoprotein has a 24-amino-acid cytoplasmic domain whose function in the viral life cycle is poorly understood. We introduced premature-stop mutations and 18 single-amino-acid substitutions into this domain and studied their effects on cell-to-cell transmission of the virus. The results show that the cytoplasmic domain is absolutely required for cell-to-cell transmission of HTLV-1, through amino acids which cluster in a Y-S-L-I tyrosine-based motif. The transmission defect in two motif mutants did not result from a defect in glycoprotein incorporation or fusion. It appears that the Y-S-L-I tyrosine-based motif of the HTLV-1 glycoprotein cytoplasmic domain has multiple functions, including involvement in virus transmission at a postfusion step.