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1.A.90 The Human Metapneumovirus (HMPV) Viroporin (HMPV-viroporin) Family

Human metapneumovirus (HMPV), first identified in 2001, is a causative agent of severe respiratory tract disease worldwide. The SH protein is one of three glycoproteins encoded by all strains of HMPV. These three glycoproteins are the G protein, which plays a role in glycosaminoglycan binding, the
fusion (F) protein, which is necessary and sufficient for both viral binding to the target cell and fusion between the cellular plasma membrane and the viral membrane, and the SH (small hydrophobic) protein, which appears to be a viroporin.

The SH protein of the closely related respiratory syncytial virus may also function as a viroporin, It forms oligomeric structures consistent with a pore and alters membrane permeability. Masante et al. (2014) showed that both the full-length HMPV SH protein and the isolated SH protein transmembrane domain can associate into higher order oligomers. In addition, HMPV SH expression resulted in increases in permeability to hygromycin B and alteration of subcellular localization of a fluorescent dye, indicating that SH affects membrane permeability. These results suggest that the HMPV SH protein has characteristics consistent with those of a viroporin.

Masante et al. (2014) also reported that expression of the HMPV SH protein can significantly decrease HMPV F protein-promoted membrane fusion activity, with the SH extracellular domain and transmembrane domain playing the key role in this inhibition. This suggests that the HMPV SH protein may regulate both membrane permeability and fusion protein function during viral infection.

Bombyx mori densovirus type 1 (BmDV) causes flacherie disease in silkworms. The nonsusceptibility to BmDV among certain silkworm strains is determined independently by two genes, nsd-1 and nid-1Ito et al. 2018 isolated the nsd-1 gene and showed that it encodes a Bombyx-specific mucin-like glycoprotein with a single TMS. The NSD-1 protein was specifically expressed in the larval midgut epithelium, the known infection site of BmDV. Sequence analysis of the nsd-1 gene from 13 resistant and 12 susceptible strains suggested that a specific arginine residue in the extracellular tail of the NSD-1 protein was common among susceptible strains. Germline transformation of the susceptible-type nsd-1 (with a single nucleotide substitution) conferred susceptibility to resistant larvae, indicating that the + (nsd-1) gene is required for the susceptibility of B. mori larvae to BmDV, and this susceptibility is solely a result of the substitution of a single amino acid with arginine. Thus, a novel membrane-bound mucin-like protein functions as a cell-surface receptor for a densovirus (Ito et al. 2018). The N-termini of these proteins resemble glutamyl aminopeptidase-like isoform X2 of Papilio xuthus (XP_013180265).

References associated with 1.A.90 family:

Ito, K., K. Kidokoro, S. Katsuma, H. Sezutsu, K. Uchino, I. Kobayashi, T. Tamura, K. Yamamoto, K. Mita, T. Shimada, and K. Kadono-Okuda. (2018). A single amino acid substitution in the Bombyx-specific mucin-like membrane protein causes resistance to Bombyx mori densovirus. Sci Rep 8: 7430. 29743532
Masante, C., F. El Najjar, A. Chang, A. Jones, C.L. Moncman, and R.E. Dutch. (2014). The human metapneumovirus small hydrophobic protein has properties consistent with those of a viroporin and can modulate viral fusogenic activity. J. Virol. 88: 6423-6433. 24672047