Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion

Toxoplasma (toxoplasmosis) and Plasmodium (malaria) use unique secretory organelles for migration, cell invasion, manipulation of host cell functions, and cell egress. In particular, the apical secretory micronemes and rhoptries of apicomplexan parasites are essential for successful host infection. New findings reveal that the contents of these organelles, which are transported through the endoplasmic reticulum (ER) and Golgi, also require the parasite endosome-like system to access their respective organelles. In this review, we discuss recent findings that demonstrate that these parasites reduced their endosomal system and modified classical regulators of this pathway for the biogenesis of apical organelles

Social Value Orientation and Endorsement of Horizontal and Vertical Individualism and Collectivism: An Exploratory Study Comparing Individuals From North America and South Korea

Individuals’ cultural tendencies of horizontal/vertical individualism and collectivism interact with their dispositional traits and contextual factors to shape social interactions. A key dispositional trait is social value orientation (SVO), a general tendency towards competition (proself) vs. cooperation (prosocial) in social exchanges. The present study (N = 1032) explored the relationship between SVO and personal cultural tendencies of horizontal/vertical individualism and collectivism in two different cultural settings, the US (a vertical individualist setting) and South Korea (a vertical collectivistic setting). We hypothesized that each value orientation would be associated with the congruent personal cultural tendency across settings. We further hypothesized that this association would be specific to the context, so that SVO would play a more relevant role where the cultural theme was less dominant. Results indicated that, across contexts, proself individuals endorsed vertical individualistic values more strongly than prosocial individuals. Conversely, prosocial individuals endorsed horizontal collectivistic values more strongly than proself individuals. In addition, the effect of SVO was different in the two cultural contexts. Compared to proself individuals, prosocial individuals endorsed horizontal collectivism more strongly in the US context, and horizontal individualism less strongly in the Korea context. Theoretical implications and limitations of the findings, as well as directions for future work are discussed

PTEX is an essential nexus for protein export in malaria parasites

During the blood stages of malaria, several hundred parasite-encoded proteins are exported beyond the double-membrane barrier that separates the parasite from the host cell cytosol. These proteins have a variety of roles that are essential to virulence or parasite growth. There is keen interest in understanding how proteins are exported and whether common machineries are involved in trafficking the different classes of exported proteins. One potential trafficking machine is a protein complex known as the Plasmodium translocon of exported proteins (PTEX). Although PTEX has been linked to the export of one class of exported proteins, there has been no direct evidence for its role and scope in protein translocation. Here we show, through the generation of two parasite lines defective for essential PTEX components (HSP101 or PTEX150), and analysis of a line lacking the non-essential component TRX2 (ref. 12), greatly reduced trafficking of all classes of exported proteins beyond the double membrane barrier enveloping the parasite. This includes proteins containing the PEXEL motif (RxLxE/Q/D) and PEXEL-negative exported proteins (PNEPs). Moreover, the export of proteins destined for expression on the infected erythrocyte surface, including the major virulence factor PfEMP1 in Plasmodium falciparum, was significantly reduced in PTEX knockdown parasites. PTEX function was also essential for blood-stage growth, because even a modest knockdown of PTEX components had a strong effect on the parasite\u27s capacity to complete the erythrocytic cycle both in vitro and in vivo. Hence, as the only known nexus for protein export in Plasmodium parasites, and an essential enzymic machine, PTEX is a prime drug target

A pathogenic picornavirus acquires an envelope by hijacking cellular membranes

Animal viruses are broadly categorized structurally by the presence or absence of an envelope composed of a lipid-bilayer membrane(1), attributes that profoundly affect stability, transmission, and immune recognition. Among those lacking an envelope, the Picornaviridae are a large and diverse family of positive-strand RNA viruses that includes hepatitis A virus (HAV), an ancient human pathogen that remains a common cause of enterically-transmitted hepatitis(2–4). HAV infects in a stealth-like manner and replicates efficiently in the liver(5). Virus-specific antibodies appear only after 3–4 weeks of infection, and typically herald its resolution(3,4). Although unexplained mechanistically, both anti-HAV antibody and inactivated whole-virus vaccines prevent disease when administered as late as 2 weeks after exposure(6), when virus replication is well established in the liver(5). Here, we show that HAV released from cells is cloaked in host-derived membranes, thereby protecting the virion from antibody-mediated neutralization. These enveloped viruses (“eHAV”) resemble exosomes(7), small vesicles that are increasingly recognized to play important roles in intercellular communications. They are fully infectious, sensitive to chloroform extraction, and circulate in the blood of infected humans. Their biogenesis is dependent upon host proteins associated with endosomal-sorting complexes required for transport (ESCRT)(8), VPS4B and ALIX. While the hijacking of membranes by HAV facilitates escape from neutralizing antibodies and likely promotes virus spread within the liver, anti-capsid antibodies restrict replication following infection with eHAV, suggesting a possible explanation for post-exposure prophylaxis. Membrane hijacking by HAV blurs the classic distinction between “enveloped” and “nonenveloped” viruses, and has broad implications for mechanisms of viral egress from infected cells as well as host immune responses