Matrix Metalloproteinase-9 and Haemozoin: Wedding Rings for Human Host andPlasmodium falciparumParasite in Complicated Malaria

It is generally accepted that the combination of bothPlasmodium falciparumparasite and human host factors is involved in the pathogenesis of complicated severe malaria, including cerebral malaria (CM). Among parasite products, the malarial pigment haemozoin (HZ) has been shown to impair the functions of mononuclear and endothelial cells. Different CM models were associated with enhanced levels of matrix metalloproteinases (MMPs), a family of proteolytic enzymes able to disrupt subendothelial basement membrane and tight junctions and shed, activate, or inactivate cytokines, chemokines, and other MMPs through cleavage from their precursors. Among MMPs, a good candidate for targeted therapy might be MMP-9, whose mRNA and protein expression enhancement as well as direct proenzyme activation by HZ have been recently investigated in a series of studies by our group and others. In the present paper the role of HZ and MMP-9 in complicated malaria, as well as their interactions, will be discussed.

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Genome-Wide RNAi Screening to Identify Human Host Factors Crucial for Influenza Virus Replication

Advances in Delivery Science and Technology - RNA Interference from Biology to Therapeutics ◽

10.1007/978-1-4614-4744-3_12 ◽

2012 ◽

pp. 243-257

Author(s):

Katharina Ahrens ◽

Alexander Karlas

Keyword(s):

Influenza Virus ◽

Virus Replication ◽

Host Factors ◽

Rnai Screening ◽

Human Host ◽

Genome Wide ◽

Influenza Virus Replication ◽

Human Host Factors

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Expansion microsopy reveals Plasmodium falciparum blood-stage parasites undergo anaphase with a chromatin bridge in the absence of mini-chromosome maintenance complex binding protein

10.1101/2021.09.25.461816 ◽

2021 ◽

Author(s):

Benjamin Liffner ◽

Sabrina Absalon

Keyword(s):

Plasmodium Falciparum ◽

Nuclear Envelope ◽

Malaria Parasite ◽

Binding Protein ◽

Nuclear Morphology ◽

Mitotic Spindles ◽

Human Host ◽

The Individual ◽

Chromatin Bridges

ABSTRACTMitosis in the malaria parasite Plasmodium falciparum undergoes closed mitosis, which occurs within an intact nuclear envelope, and differs significantly from its human host. Mitosis is underpinned by the dynamics of microtubules and the nuclear envelope. To date, our ability to study P. falciparum mitosis by microscopy has been hindered by the small size of P. falciparum nuclei. Ultrastructure expansion microscopy (U-ExM) has recently been developed for P. falciparum, allowing visualization of mitosis at the individual nucleus level. Using U-ExM, three intranuclear microtubule structures are observed: hemispindles, mitotic spindles and interpolar spindles. A previous study demonstrated that the mini-chromosome maintenance complex binding-protein (MCMBP) depletion caused abnormal nuclear morphology and microtubule defects. To investigate the role of microtubules following MCMBP depletion and study the nuclear envelope in these parasites, we developed the first nuclear stain enabled by U-ExM in P. falciparum. MCMBP deficient parasites show aberrant hemispindles and mitotic spindles. Moreover, anaphase chromatin bridges, and individual nuclei containing multiple microtubule structures were observed following MCMBP knockdown. Collectively, this study refines our model for the phenotype of MCMBP-deficient parasites and highlights the utility of U-ExM coupled with a nuclear envelope stain for studying mitosis in P. falciparum.

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Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication

Nature ◽

10.1038/nature08760 ◽

2010 ◽

Vol 463 (7282) ◽

pp. 818-822 ◽

Cited By ~ 473

Author(s):

Alexander Karlas ◽

Nikolaus Machuy ◽

Yujin Shin ◽

Klaus-Peter Pleissner ◽

Anita Artarini ◽

...

Keyword(s):

Influenza Virus ◽

Virus Replication ◽

Rnai Screen ◽

Host Factors ◽

Human Host ◽

Genome Wide ◽

Influenza Virus Replication ◽

Human Host Factors

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Visual Genome-Wide RNAi Screening to Identify Human Host Factors Required for Trypanosoma cruzi Infection

PLoS ONE ◽

10.1371/journal.pone.0019733 ◽

2011 ◽

Vol 6 (5) ◽

pp. e19733 ◽

Cited By ~ 24

Author(s):

Auguste Genovesio ◽

Miriam A. Giardini ◽

Yong-Jun Kwon ◽

Fernando de Macedo Dossin ◽

Seo Yeon Choi ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Host Factors ◽

Rnai Screening ◽

Human Host ◽

Genome Wide ◽

Human Host Factors ◽

Cruzi Infection

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Modelling cytomegalovirus replication patterns in the human host: factors important for pathogenesis

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2006.3506 ◽

2006 ◽

Vol 273 (1596) ◽

pp. 1961-1967 ◽

Cited By ~ 14

Author(s):

Roland R Regoes ◽

E Frances Bowen ◽

Alethea V Cope ◽

Dehila Gor ◽

Aycan F Hassan-Walker ◽

...

Keyword(s):

Host Factors ◽

Human Host ◽

Human Host Factors

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Preliminary Study on Human Host Factors Perpetuating the Transmission of Schistosomiasis in Endemic Community of Wudil, Kano State, Nigeria

Annual Research & Review in Biology ◽

10.9734/arrb/2021/v36i830408 ◽

2021 ◽

pp. 27-41

Author(s):

Mahmud Ali Umar ◽

Umar Aliyu Umar ◽

Mujitapha Lawal ◽

Sani Muhammad Yahaya ◽

Muhammad Salisu Inuwa

Keyword(s):

Salt Intake ◽

Strong Association ◽

Host Factors ◽

Water Contact ◽

Disease Etiology ◽

Riverine Water ◽

Human Host ◽

Study Participants ◽

Human Host Factors ◽

Gross Haematuria

Objective: A cross-sectional study was conducted to determine the human host factors that contribute to the perpetuation of schistosomiasis transmission in endemic communities of Wudil, Kano State, Nigeria. Methods: Information was derived from structured questionnaires supplemented with oral interviews, on perception of the community on the cause of urogenital schistosomiasis, using self-reported macrohaematuria, as the disease proxy, water-use practices, riverside urination and defaecation, and the choice for treatment of schistosome infection. Results: Out of 139 study participants, the perceived causes of gross haematuria by the respondents were Excessive Salt Intake (41.73%); Scorching Sun (20.86%); Unknown (17.27%); Infection (10.07%); Supernatural Force (5.86%) and Water Contact (4.32%). The respondents with self-reported terminal haematuria were 49.64%; riverine water contact 75.54% and riverside contamination 65.41%. Of the 72.46% of the respondents with gross haematuria who attempted for medication only 8.0% visited health facilities, while majority relied on traditional herbalists (39.13%) and roadside medicine stores (20.29%) for treatment. There was a strong association between riverine water contact and terminal haematuria (Odds Ratio: 6.09, 95% CI, 2.825-13.131, P<0.0001; Relative Risk: 2.737, 95% CI, 1.664-4.502, P<0.0001). Conclusion: Exposure to contaminated water as a result of socioeconomic activities, riverside, poor perception on the cause of the disease and lack of adherence to orthodox treatment of positive cases are the key promoters of schistosomiasis transmission in the study area. Excessive salt intake and scorching sun are the major perceived causes of haematuria among the study participants. This underpins the need for health education and other efficacious interventions for community awareness on the disease etiology which is central to effective elimination campaign.

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Human host factors required for influenza virus replication

Nature ◽

10.1038/nature08699 ◽

2009 ◽

Vol 463 (7282) ◽

pp. 813-817 ◽

Cited By ~ 557

Author(s):

Renate König ◽

Silke Stertz ◽

Yingyao Zhou ◽

Atsushi Inoue ◽

H. -Heinrich Hoffmann ◽

...

Keyword(s):

Influenza Virus ◽

Virus Replication ◽

Host Factors ◽

Human Host ◽

Influenza Virus Replication ◽

Human Host Factors

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Conserved Genomic Terminals of SARS-CoV-2 as Coevolving Functional Elements and Potential Therapeutic Targets

mSphere ◽

10.1128/msphere.00754-20 ◽

2020 ◽

Vol 5 (6) ◽

Author(s):

Agnes P. Chan ◽

Yongwook Choi ◽

Nicholas J. Schork

Keyword(s):

Drug Targets ◽

Influenza A ◽

Therapeutic Targets ◽

Target Prediction ◽

Host Factors ◽

Human Host ◽

Host Interaction ◽

Study Results ◽

Influenza A H1n1 ◽

Human Host Factors

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 40 million people worldwide, with over 1 million deaths as of October 2020 and with multiple efforts in the development and testing of antiviral drugs and vaccines under way. In order to gain insights into SARS-CoV-2 evolution and drug targets, we investigated how and to what extent the SARS-CoV-2 genome sequence differs from those of other well-characterized human and animal coronavirus genomes, as well as how polymorphic SARS-CoV-2 genomes are generally. We ultimately sought to identify features in the SARS-CoV-2 genome that may contribute to its viral replication, host pathogenicity, and vulnerabilities. Our analyses suggest the presence of unique sequence signatures in the 3′ untranslated region (3′-UTR) of betacoronavirus lineage B, which phylogenetically encompasses SARS-CoV-2 and SARS-CoV as well as multiple groups of bat and animal coronaviruses. In addition, we identified genome-wide patterns of variation across different SARS-CoV-2 strains that likely reflect the effects of selection. Finally, we provide evidence for a possible host-microRNA-mediated interaction between the 3′-UTR and human microRNA hsa-miR-1307-3p based on the results of multiple computational target prediction analyses and an assessment of similar interactions involving the influenza A H1N1 virus. This interaction also suggests a possible survival mechanism, whereby a mutation in the SARS-CoV-2 3′-UTR leads to a weakened host immune response. The potential roles of host microRNAs in SARS-CoV-2 replication and infection and the exploitation of conserved features in the 3′-UTR as therapeutic targets warrant further investigation. IMPORTANCE The coronavirus disease 2019 (COVID-19) outbreak is having a dramatic global effect on public health and the economy. As of October 2020, SARS-CoV-2 has been detected in over 189 countries, has infected over 40 million people, and is responsible for more than 1 million deaths. The genome of SARS-CoV-2 is small but complex, and its functions and interactions with human host factors are being studied extensively. The significance of our study is that, using extensive SARS-CoV-2 genome analysis techniques, we identified potential interacting human host microRNA targets that share similarity with those of influenza A virus H1N1. Our study results will allow the development of virus-host interaction models that will enhance our understanding of SARS-CoV-2 pathogenesis and motivate the exploitation of both the interacting viral and host factors as therapeutic targets.

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