Ul131aEdit

UL131A is a gene in the genome of the human cytomegalovirus (HCMV) that encodes a small membrane glycoprotein and plays a pivotal role in the virus’s entry machinery. In the context of HCMV biology, UL131A is best known as a component of the pentameric complex formed with glycoproteins gH and gL and the accessory subunits UL128 and UL130. This complex, often referred to as the gH/gL/UL128-UL131A pentamer, is essential for efficient entry into certain human cell types, particularly epithelial and endothelial cells, as well as some myeloid cells. By contrast, entry into fibroblasts can occur in the absence of the pentamer, illustrating how UL131A shapes tissue tropism and pathogenesis. The study of UL131A and its companions has clarified why some CMV strains disseminate differently within the host and why congenital CMV disease can involve tissues beyond the placenta.

UL131A in the genome and its protein product - Genomic context: UL131A resides in the UL128-UL131A region of the HCMV genome, a cluster implicated in defining the virus’s cell-type range. The locus also includes other components that cooperate to form the pentameric complex. Researchers often discuss this region as a determinant of epithelial, endothelial, and myeloid tropism. UL128-UL131A - Protein product and role: The UL131A gene product is a type I membrane glycoprotein that participates in assembling the pentameric complex with gH and gL and the UL128 and UL130 subunits. The resulting pentamer is distinct from the gH/gL/gB trimeric complex and is required for efficient entry into certain cell types. The exact receptor engagements and molecular interfaces are an active area of investigation, but the functional consequence is clear: the pentamer broadens CMV’s cellular reach beyond fibroblasts. Related glycoproteins and their interactions are discussed in entries on glycoprotein H and glycoprotein L as well as the broader concept of the pentameric complex.

Impact on cell tropism and entry - Differential entry pathways: HCMV can utilize at least two entry routes. The gH/gL/gB trimeric complex supports entry into some cell types, including fibroblasts, under certain conditions. The additional pentamer formed with UL128-UL131A expands this repertoire to epithelial and endothelial cells, as well as some hematopoietic cells. Thus, UL131A is a key determinant of which tissues the virus can efficiently infect. epithelial cells, endothelial cells, myeloid cells - Consequences for pathogenesis: Strains carrying a functional UL128-UL131A region—and therefore the pentamer—toster more effectively disseminate through tissues and may contribute to placental crossing and fetal involvement in congenital CMV infections. By contrast, laboratory-adapted CMV strains that have deletions or mutations in this region show restricted tropism, primarily infecting fibroblasts in vitro. This distinction has shaped how scientists study CMV biology in the lab versus in human disease. See discussions of specific laboratory strains such as AD169 for historical context.

Clinical and translational significance - Congenital CMV disease: The ability of HCMV to infect placental and fetal tissues is partly linked to the +UL128-UL131A pentameric complex; neutralizing antibodies and vaccines that target this pentamer have been a major focus because of its central role in epithelial and endothelial entry. Investigations into UL131A and the pentamer inform strategies to reduce transplacental transmission or fetal organ involvement. congenital cytomegalovirus - Vaccine and therapeutics: The pentameric complex is a prime antigen for vaccine development and for designing neutralizing antibody therapies. Vaccines or monoclonal antibodies that elicit or supply potent responses against gH/gL/UL128-UL131A can block entry into the most export-risk cell types, complementing other targets like the gB glycoprotein. This has influenced ongoing research programs and clinical trial designs. Related topics include neutralizing antibody and vaccine development in the context of CMV. - Strain variation and research implications: Natural CMV strains vary in the integrity of the UL128-UL131A locus. Laboratory-passaged strains that lose this region show reduced epithelial/endothelial tropism, which is a cautionary note for interpreting in vitro experiments and for understanding why some preclinical models may underrepresent tissue dissemination seen in patients. Readers may encounter discussions of specific strains such as AD169 and other clinical isolates when considering tropism and pathogenesis.

Evolution, diversity, and comparative biology - Genetic diversity: The UL128-UL131A locus exhibits variability across CMV strains, reflecting adaptation to different host environments and selective pressures tied to tissue tropism and immune evasion. The balance between maintaining a functional pentamer and the costs of expressing or mutating these components shapes how CMV evolves in human populations. Comparative analyses with other herpesviruses show convergent strategies around entry glycoproteins and receptor engagement.

See also - human cytomegalovirus - AD169 - glycoprotein H - glycoprotein L - glycoprotein B - pentameric complex - congenital cytomegalovirus