Inés García-Rodríguez

Ms. Inés García-Rodríguez

1OrganoVIR Lab, Department of Medical Microbiology, Amsterdam UMC, location Academic Medical Center, University of Amsterdam, 1100 AZ Amsterdam, The Netherlands;
+1
orcid

Research Focus & Metrics

Academic Career Length

7Years (2020-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

View All Publications
11 November 2020 in Viruses
Verified
Journal Article
Open access
PDF file
Inés García-RodríguezInés García-Rodríguez
Inés García-Rodríguez
ASAdithya Sridhar
Adithya Sridhar
DPDasja Pajkrt
Dasja Pajkrt
KWKatja C. Wolthers
Katja C. Wolthers
The knowledge about enteric viral infection has vastly increased over the last eight years due to the development of intestinal organoids and enteroids that suppose a step forward from conventional studies using cell lines. Intestinal organoids and enteroids are three-dimensional (3D) models that closely mimic intestinal cellular heterogeneity and organization. The barrier function within these models has been adapted to facilitate viral studies. In this review, several adaptations (such as organoid-derived two-dimensional (2D) monolayers) and original intestinal 3D models are discussed. The specific advantages and applications, as well as improvements of each model are analyzed and an insight into the possible path for the field is given.

21 March 2024 in Nature Communications
Verified
Journal Article
Open access
PDF file
PCPamela E. Capendale
Pamela E. Capendale
Inés García-RodríguezInés García-Rodríguez
Inés García-Rodríguez
AAAnoop T. Ambikan
Anoop T. Ambikan
LMLance A. Mulder
Lance A. Mulder
JDJosse A. Depla
Josse A. Depla
KWKatja C. Wolthers
Katja C. Wolthers
Picornaviruses are a leading cause of central nervous system (CNS) infections. While genotypes such as parechovirus A3 (PeV-A3) and echovirus 11 (E11) can elicit severe neurological disease, the highly prevalent PeV-A1 is not associated with CNS disease. Here, we expand our current understanding of these differences in PeV-A CNS disease using human brain organoids and clinical isolates of the two PeV-A genotypes. Our data indicate that PeV-A1 and A3 specific differences in neurological disease are not due to infectivity of CNS cells as both viruses productively infect brain organoids with a similar cell tropism. Proteomic analysis shows that PeV-A infection significantly alters the host cell metabolism. The inflammatory response following PeV-A3 (and E11 infection) is significantly more potent than that upon PeV-A1 infection. Collectively, our findings align with clinical observations and suggest a role for neuroinflammation, rather than viral replication, in PeV-A3 (and E11) infection.

1 November 2021 in Frontiers in Cellular and Infection Microbiology
Verified
Journal Article
Open access
Inés García-RodríguezInés García-Rodríguez
Inés García-Rodríguez
HEHetty van Eijk
Hetty van Eijk
GKGerrit Koen
Gerrit Koen
DPDasja Pajkrt
Dasja Pajkrt
ASAdithya Sridhar
Adithya Sridhar
KWKatja C. Wolthers
Katja C. Wolthers
Human parechovirus (PeV-A), one of the species within the Picornaviridae family, is known to cause disease in humans. The most commonly detected genotypes are PeV-A1, associated with mild gastrointestinal disease in young children, and PeV-A3, linked to severe disease with neurological symptoms in neonates. As PeV-A are detectable in stool and nasopharyngeal samples, entry is speculated to occur via the respiratory and gastro-intestinal routes. In this study, we characterized PeV-A1 and PeV-A3 replication and tropism in the intestinal epithelium using a primary 2D model based on human fetal enteroids. This model was permissive to infection with lab-adapted strains and clinical isolates of PeV-A1, but for PeV-A3, infection could only be established with clinical isolates. Replication was highest with infection established from the basolateral side with apical shedding for both genotypes. Compared to PeV-A1, replication kinetics of PeV-A3 were slower. Interestingly, there was a difference in cell tropism with PeV-A1 infecting both Paneth cells and enterocytes, while PeV-A3 infected mainly goblet cells. This difference in cell tropism may explain the difference in replication kinetics and associated disease in humans.

4 August 2022 in Life Science Alliance
Verified
Journal Article
Open access
PDF file
IAIkrame Aknouch
Ikrame Aknouch
ASAdithya Sridhar
Adithya Sridhar
EFEline Freeze
Eline Freeze
FGFrancesca Paola Giugliano
Francesca Paola Giugliano
BKBritt J van Keulen
Britt J van Keulen
DPDasja Pajkrt
Dasja Pajkrt
Human milk is important for antimicrobial defense in infants and has well demonstrated antiviral activity. We evaluated the protective ability of human milk against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a human fetal intestinal cell culture model. We found that, in this model, human milk blocks SARS-CoV-2 replication, irrespective of the presence of SARS-CoV-2 spike-specific antibodies. Complete inhibition of both enveloped Middle East respiratory syndrome coronavirus and human respiratory syncytial virus infections was also observed, whereas no inhibition of non-enveloped enterovirus A71 infection was seen. Transcriptome analysis after 24 h of the intestinal monolayers treated with human milk showed large transcriptomic changes from human milk treatment, and subsequent analysis suggested thatATP1A1down-regulation by milk might be of importance. Inhibition of ATP1A1 blocked SARS-CoV-2 infection in our intestinal model, whereas no effect on EV-A71 infection was seen. Our data indicate that human milk has potent antiviral activity against particular (enveloped) viruses by potentially blocking the ATP1A1-mediated endocytic process.

9 May 2022 in Viruses
Verified
Journal Article
Open access
PDF file
CRCarmen Rodriguez
Carmen Rodriguez
Inés García-RodríguezInés García-Rodríguez
Inés García-Rodríguez
CNCallum Baird Nattress
Callum Baird Nattress
AQAhad Qureshi
Ahad Qureshi
Gunnel HalldénGunnel Halldén
Gunnel Halldén
The prognosis for triple-negative breast cancer (TNBC) and pancreatic ductal adenocarcinoma (PDAC) is dismal. TNBC and PDAC are highly aggressive cancers with few treatment options and a potential for rapid resistance to standard-of-care chemotherapeutics. Oncolytic adenoviruses (OAds) represent a promising tumour-selective strategy that can overcome treatment resistance and eliminate cancer cells by lysis and host immune activation. We demonstrate that histone deacetylase inhibitors (HDACi) potently enhanced the cancer-cell killing of our OAds, Ad∆∆ and Ad-3∆-A20T in TNBC and PDAC preclinical models. In the TNBC cell lines MDA-MB-436, SUM159 and CAL51, cell killing, viral uptake and replication were increased when treated with sublethal doses of the Class-I-selective HDACis Scriptaid, Romidepsin and MS-275. The pan-HDACi, TSA efficiently improved OAd efficacy, both in vitro and in SUM159 xenograft models in vivo. Cell killing and Ad∆∆ replication was also significantly increased in five PDAC cell lines when pre-treated with TSA. Efficacy was dependent on treatment time and dose, and on the specific genetic alterations in each cell line. Expression of the cancer specific αvß6-integrin supported higher viral uptake of the integrin-retargeted Ad-3∆-A20T in combination with Scriptaid. In conclusion, we demonstrate that inhibition of specific HDACs is a potential means to enhance OAd activity, supporting clinical translation.

6 January 2024 in Antiviral Research
Verified
Journal Article
Open access
Inés García-RodríguezInés García-Rodríguez
Inés García-Rodríguez
Giulia MoreniGiulia Moreni
Giulia Moreni
PCPamela E. Capendale
Pamela E. Capendale
LMLance Mulder
Lance Mulder
IAIkrame Aknouch
Ikrame Aknouch
CCCarlemi Calitz
Carlemi Calitz
Halofuginone hydrobromide has shown potent antiviral efficacy against a variety of viruses such as SARS-CoV-2, dengue, or chikungunya virus, and has, therefore, been hypothesized to have broad-spectrum antiviral activity. In this paper, we tested this broad-spectrum antiviral activity of Halofuginone hydrobomide against viruses from different families (Picornaviridae, Herpesviridae, Orthomyxoviridae, Coronaviridae, and Flaviviridae). To this end, we used relevant human models of the airway and intestinal epithelium and regionalized neural organoids. Halofuginone hydrobomide showed antiviral activity against SARS-CoV-2 in the airway epithelium with no toxicity at equivalent concentrations used in human clinical trials but not against any of the other tested viruses.