Biology subjects

Hu, C. T.

Publications and source records attributed to Hu, C. T..

3 recordsLinked to original sources

bioRxiv2026

SIRPA suppresses integrin-dependent virus endocytosis

New World arenaviruses (NWAs) that cause viral hemorrhagic fever, such as Junin virus, have few therapeutic options. Entry of these viruses into cells is mediated by binding to cell surface receptors, followed by endocytosis and trafficking to a low pH compartment. We showed previously that Signal Regulatory Protein Alpha (SIRPA), a critical cell surface receptor that inhibits macrophage phagocytic activity, decreases internalization by NWAs as well as other pathogenic RNA viruses that traffic to low pH compartments. Here we demonstrate that proteins involved in the SIRPA/integrin signaling axis, including Src homology region 2 (SH2)-containing protein tyrosine phosphatase 2 (SHP2), src family kinases (SFKs), particularly FYN, focal adhesion kinase (FAK), and alpha-integrin play a role in viral endocytosis and that SIRPA inhibits virus entry through blocking this pathway. In addition to defining a role for integrins in viral entry, these studies also provide additional insight into SIRPAs interference in processes dependent on integrin signaling, including phagocytosis. Moreover, using drugs that block the integrin signaling pathway in vitro and in vivo, we show that there are additional steps that may be targeted therapeutically for inhibiting infection by RNA viruses that traffic to acidic compartments.

cell biology↗

bioRxiv2021

Friend or Foe: Hybrid proline-rich proteins determine how plants interact with and respond to beneficial and pathogenic microbes

Plant plastids generate signals, including some derived from lipids, that need to be mobilized to effect signaling. We used informatics to discover potential plastid membrane proteins involved in microbial responses. Among these are proteins co-regulated with the systemic immunity component AZI1, a hybrid proline-rich protein (HyPRP) and HyPRP superfamily members. HyPRPs have a transmembrane domain, a proline-rich region (PRR) and a lipid transfer protein domain. The precise subcellular location(s) and function(s) is unknown for most HyPRP family members. As predicted by informatics, a subset of HyPRPs have a pool of protein that targets plastid outer envelope membranes (OEMs) via a mechanism that requires the PRR. Additionally, two HyPRPs may be associated with thylakoid membranes. Most of the plastid and non-plastid localized family members also have pools that localize to endoplasmic reticulum, plasma membrane or plasmodesmata. HyPRPs with plastid pools regulate, positively or negatively, systemic immunity against the pathogen Pseudomonas syringae. HyPRPs also regulate the interaction with the plant growth promoting rhizobacteria Pseudomonas simiae WCS417 in the roots to influence colonization, root system architecture and/or biomass. Thus, HyPRPs have broad and distinct roles in immune, development and growth responses to microbes and reside at sites that may facilitate signal molecule transport.

plant biology↗

bioRxiv2020

Defensin driven viral evolution

Enteric alpha-defensins are potent effectors of innate immunity that are abundantly expressed in the small intestine. Certain enteric bacteria and viruses are resistant to defensins and even appropriate them to enhance infection, despite neutralization of closely related microbes. We therefore hypothesized that defensins impose selective pressure during fecal-oral transmission. Upon passaging a defensin-sensitive serotype of adenovirus in the presence of a human defensin, mutations in the major capsid protein hexon accumulated. In contrast, prior studies identified the vertex proteins as important determinants of defensin antiviral activity. Through infection and biochemical assays, we found that although all major capsid proteins serve a critical role in defensin-mediated neutralization, hexon is the sole determinant of enhancement. These results extensively revise our understanding of the interplay between defensins and non-enveloped viruses. Furthermore, they provide a feasible rationale for defensins shaping viral evolution, resulting in differences in infection phenotypes of closely related viruses. Author SummaryDefensins are potent antimicrobial peptides that are found on human mucosal surfaces and can directly neutralize viruses. They are abundant in the small intestine, which is constantly challenged by ingested viral pathogens. Interestingly, non-enveloped viruses, such as adenovirus, that infect the gastrointestinal system are unaffected by defensins or can even appropriate defensins to enhance their infection. In contrast, respiratory adenoviruses are neutralized by the same defensins. How enteric viruses overcome defensin neutralization is not well understood. Our studies are the first to show that defensins can drive the evolution of non-enveloped viruses. Furthermore, we identify important components within human adenovirus that dictate sensitivity to defensins. This refined understanding of defensin-virus interactions informs the development of defensin-based therapeutics.

microbiology↗