Comparative Review of the Conserved UL24 Protein Family in Herpesviruses

Abstract

The UL24 protein family, conserved across all subfamilies of Orthoherpesviridae, plays diverse and significant roles in viral replication, host-virus interactions and pathogenesis. Understanding the molecular mechanisms and interactions of UL24 proteins is key to unraveling the complex interplay between herpesviruses and their hosts. This review provides a comparative and comprehensive overview of current knowledge on UL24 family members, including their conservation, expression patterns, cellular localization, and functional roles upon their expression and during viral infection, highlighting their significance in herpesvirus biology and their potential functions.

Keywords: ORF35; UL24; UL76; herpesvirus; open reading frame 20 (ORF20).

Figure 1

Predicted structures of proteins from the UL24 family across nine human herpesviruses, generated using the AlphaFold2 AI system. (A) Cartoon models of the predicted structures for HSV-1 UL24, HSV-2 UL24, VZV ORF35, HCMV UL76, HHV-6A U49, HHV-6B U49, HHV-7 UL24, EBV BXRF1, and KSHV ORF20 are shown from the same angle. The homology domains (HDs) are color-coded as follows: HD-1—orange, HD-2—yellow, HD-3—green, HD-4—blue, and HD-5—pink. The putative endonuclease motif is highlighted in red as a stick model. (B) A table summarizing the local distance difference test (pLDDT) confidence scores.