Structure guided mutagenesis of Henipavirus Receptor Binding Proteins reveals molecular determinants of receptor usage and antibody binding epitopes.

Nipah virus (NiV) is a highly lethal, zoonotic henipavirus (HNV) that causes respiratory and neurological signs and symptoms in humans. Similar to other paramyxoviruses, HNVs mediate entry into host cells through the concerted actions of two surface glycoproteins: a receptor binding protein (RBP) that mediates attachment and a fusion glycoprotein (F) that triggers fusion in an RBP-dependent manner. NiV uses ephrin-B2 (EFNB2) and ephrin-B3 (EFNB3) as entry receptors. Ghana virus (GhV), a novel HNV identified in a Ghanaian bat, use EFNB2 but not EFNB3. In this study, we employ a structure-informed approach to identify receptor interfacing residues and systematically introduce GhV-RBP residues into a NiV-RBP backbone to uncover the molecular determinants of EFNB3 usage. We reveal two regions that severely impair EFNB3 binding by NiV-RBP and EFNB3-mediated entry by NiV pseudotyped viral particles. Further analyses uncovered two point mutations (NiVN557SGhV and NiVY581TGhV) pivotal for this phenotype. Moreover, we identify NiV interaction with Y120 of EFNB3 as important for usage of this receptor. Beyond these EFNB3-related findings, we reveal two domains that restrict GhV binding of EFNB2, identify the HNV-head as an immunodominant target for polyclonal and monoclonal antibodies, and describe putative epitopes for GhV and NiV-specific monoclonal antibodies. Cumulatively, the work presented here generates useful reagents and tools that shed insight to residues important for NiV usage of EFNB3, reveals regions critical for GhV binding of EFNB2, and describes putative HNV antibody binding epitopes.

Eccrine syringofibroadenoma (Mascaró). An acrosyringeal hamartoma.

Two patients with eccrine syringofibroadenomas were studied. The first patient had a 3-year history of asymptomatic, unilateral, linear, moist mosaic plaques of the lower part of the left leg and foot; the second patient had a solitary papule on the back. Histologically, both tumors exhibited superficial elongated strands of eccrine ductal epithelium containing occasional lumina lined by an eosinophilic cuticle. The stroma was loose, myxoid, and fibrovascular. The secretory portions of the eccrine glands were ectatic in the first patient but were not seen in the second patient. We believe these lesions represent acrosyringeal hamartomas (nevi), although some authors interpret them as adenomas. The literature seems to indicate that lesions with similar histologic features may be solitary, multiple, or combined with other neoplasms; in other cases, the lesions may possibly represent an unusual morphologic expression of hidrotic ectodermal dysplasia.

Lupus vulgaris: a case that escaped diagnosis for twenty-eight years.

Lupus vulgaris is uncommon in the United States and occasionally goes unrecognized for years before the diagnosis is made. A 65-year-old Mexican-American man with disseminated tuberculosis was discovered to have a large annular lesion of lupus vulgaris on his buttocks and thighs. The lesion had been present and slowly enlarging for twenty-eight years. The clinical and histologic features of primary inoculation tuberculosis and reinfection tuberculosis of the skin are reviewed.

Bowenoid papules of the genitalia. A case progressing to Bowen's disease.

We report a case of an older man with bowenoid papulosis of the genitalia progressing to a plaque of carcinoma in situ. The case also demonstrates a progressive eruption of bowenoid papules over a 10-year period.