Interaction of an atypical Plasmodium falciparum ETRAMP with human apolipoproteins

Vignali, Marissa; McKinlay, Anastasia; LaCount, Douglas; Chettier, Rakesh; Bell, Russell; Sahasrabudhe, Sudhir; Hughes, Robert E.; Fields, Stanley

doi:10.1186/1475-2875-7-211

Cited by 40 publications

(48 citation statements)

References 40 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All inserts were verified by PCR and sequencing. DENV DNAbinding domain constructs were screened against a human liver yeast two-hybrid library cloned into the activation domain plasmid pOAD.103 in yeast strain BK100 (MATa ura3-52 ade2-101 trp1-901 leu2-3,112 his3-200 gal4⌬ gal80⌬ GAL2-ADE2 LYS2::GAL1-HIS3 met2::GAL7-lacZ, a derivative of PJ69 -4A) (43,47,48). The original library contained 9.6 ϫ 10 5 independent clones with an average insert size of 840 bp.…”

Section: Methodsmentioning

confidence: 99%

A Physical Interaction Network of Dengue Virus and Human Proteins

Khadka

Vangeloff

Zhang

et al. 2011

Molecular & Cellular Proteomics

Self Cite

153

148

View full text Add to dashboard Cite

Dengue virus (DENV), an emerging mosquito-transmitted pathogen capable of causing severe disease in humans, interacts with host cell factors to create a more favorable environment for replication. However, few interactions between DENV and human proteins have been reported to date. To identify DENV-human protein interactions, we used high-throughput yeast two-hybrid assays to screen the 10 DENV proteins against a human liver activation domain library. From 45 DNA-binding domain clones containing either full-length viral genes or partially overlapping gene fragments, we identified 139 interactions between DENV and human proteins, the vast majority of which are novel. These interactions involved 105 human proteins, including six previously implicated in DENV infection and 45 linked to the replication of other viruses. Human proteins with functions related to the complement and coagulation cascade, the centrosome, and the cytoskeleton were enriched among the DENV interaction partners. To determine if the cellular proteins were required for DENV infection, we used small interfering RNAs to inhibit their expression. Six of 12 proteins targeted (CALR, DDX3X, ERC1, GOLGA2, TRIP11, and UBE2I) caused a significant decrease in the replication of a DENV replicon. We further showed that calreticulin colocalized with viral dsRNA and with the viral NS3 and NS5 proteins in DENV-infected cells, consistent with a direct role for calreticulin in DENV replication. Human proteins that interacted with DENV had significantly higher average degree and betweenness than expected by chance, which provides additional support for the hypothesis that viruses preferentially target cellular proteins that occupy central position in the human protein interaction network. This study provides a valuable starting point for additional investigations into the roles of human proteins in

show abstract

Section: Methodsmentioning

confidence: 99%

A Physical Interaction Network of Dengue Virus and Human Proteins

Khadka

Vangeloff

Zhang

et al. 2011

Molecular & Cellular Proteomics

Self Cite

153

148

View full text Add to dashboard Cite

show abstract

“…Although another two ETRAMPs of the human malaria parasite, P. falciparum (Pf), are known to bind host-cell proteins, the function of these protein-protein interactions and that of most PVM-resident proteins remains largely elusive (26,27).…”

Section: Significancementioning

confidence: 99%

Plasmodium berghei EXP-1 interacts with host Apolipoprotein H during Plasmodium liver-stage development

Cunha

Nyboer

Heiß

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The first, obligatory replication phase of malaria parasite infections is characterized by rapid expansion and differentiation of single parasites in liver cells, resulting in the formation and release of thousands of invasive merozoites into the bloodstream. Hepatic Plasmodium development occurs inside a specialized membranous compartment termed the parasitophorous vacuole (PV). Here, we show that, during the parasite's hepatic replication, the C-terminal region of the parasitic PV membrane protein exported protein 1 (EXP-1) binds to host Apolipoprotein H (ApoH) and that this molecular interaction plays a pivotal role for successful Plasmodium liver-stage development. Expression of a truncated EXP-1 protein, missing the specific ApoH interaction site, or down-regulation of ApoH expression in either hepatic cells or mouse livers by RNA interference resulted in impaired intrahepatic development. Furthermore, infection of mice with sporozoites expressing a truncated version of EXP-1 resulted in both a significant reduction of liver burden and delayed blood-stage patency, leading to a disease outcome different from that generally induced by infection with wildtype parasites. This study identifies a host-parasite protein interaction during the hepatic stage of infection by Plasmodium parasites. The identification of such vital interactions may hold potential toward the development of novel malaria prevention strategies. malaria | Plasmodium liver stages | host-parasite interaction | ApoH | EXP-1

show abstract

“…Furthermore, Dyer et al compared experimentally known interactions of different viruses with the human host (20). The first small map of experimentally determined protein interactions between the human host and the malaria parasite P. falciparum was released recently (21), and was preceded by computational predictions of host-parasite interactions (22,23).…”

mentioning

confidence: 99%

“…Combining these interactions with experimentally determined (21) and previously predicted interactions based on protein structural features (22,23), we pooled a large set of host-parasite interactions. Although completely different in their biology and evolution, we find that both HIV-1 and P. falciparum use their protein repertoires in a combinatorial manner.…”

mentioning

confidence: 99%

Shared Molecular Strategies of the Malaria Parasite P. falciparum and the Human Virus HIV-1

Wuchty

Siwo

Ferdig

2011

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

We augmented existing computationally predicted and experimentally determined interactions with evolutionarily conserved interactions between proteins of the malaria parasite, P. falciparum, and the human host. In a validation step, we found that conserved interacting hostparasite protein pairs were specifically expressed in host tissues where both the parasite and host proteins are known to be active. We compared host-parasite interactions with experimentally verified interactions between human host proteins and a very different pathogen, HIV-1. Both pathogens were found to use their protein repertoire in a combinatorial manner, providing a broad connection to host cellular processes. Specifically, the two biologically distinct pathogens predominately target central proteins to take control of a human host cell, effectively reaching into diversified cellular host cellular functions. Interacting signaling pathways and a small set of regulatory and signaling proteins were prime targets of both pathogens, suggesting remarkably similar patterns of host-pathogen interactions despite the vast biological differences of both pathogens. Such an identification of shared molecular strategies by the virus HIV-1 and the eukaryotic intracellular pathogen P. falciparum may allow us to illuminate new avenues of disease intervention.

show abstract

Interaction of an atypical Plasmodium falciparum ETRAMP with human apolipoproteins

Cited by 40 publications

References 40 publications

A Physical Interaction Network of Dengue Virus and Human Proteins

A Physical Interaction Network of Dengue Virus and Human Proteins

Plasmodium berghei EXP-1 interacts with host Apolipoprotein H during Plasmodium liver-stage development

Shared Molecular Strategies of the Malaria Parasite P. falciparum and the Human Virus HIV-1

Contact Info

Product

Resources

About