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Displaying One Session

Session Type
Workshop Session
Date
07/20/2022
Session Time
07:00 PM - 08:30 PM
Room
Hall 1
Chair(s)
  • M. Lamers (Netherlands)

Pathogenesis of Viral Diseases

Session Type
Workshop Session
Date
07/20/2022
Session Time
07:00 PM - 08:30 PM
Room
Hall 1
Presenter
  • M. Lamers (Netherlands)
Lecture Time
07:00 PM - 07:30 PM

ORGAN-SPECIFIC THREE-DIMENSIONAL VESSEL-ON-CHIP MODELS TO STUDY ORTHOHANTAVIRUS PATHOGENESIS

Session Type
Workshop Session
Date
07/20/2022
Session Time
07:00 PM - 08:30 PM
Room
Hall 1
Presenter
  • D. Noack (Netherlands)
Lecture Time
07:30 PM - 07:40 PM

Abstract

Background and Aims

Orthohantaviruses are emerging zoonotic viruses with rodents as their main reservoir. Upon respiratory transmission, human infection can result in hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS) depending on the causative virus. Endothelial cells are predominantly infected with endothelial cell activation and increased vascular permeability likely to play a central role in pathogenesis. Although microvasculature of multiple organs can become infected, distinct clinical outcomes between HFRS and HCPS exist. Endothelial cells cultured in conventional static two-dimensional conditions are physiologically not representative due to their lack of shear-stress and their inherent pro-inflammatory state. Novel culturing platforms that allow endothelial cell culture under these physiological conditions are needed to unravel organ-specific vascular host responses.

Methods

Here, we present novel organ-specific three-dimensional primary endothelial vessel-on-chip microfluidic models for studying orthohantavirus infection. We established a high-throughput method for culturing these vessels originating from lungs, kidney, liver, heart, skin and umbilical vein.

Results

Upon TNFα-stimulation, endothelial cell activation leads to increases of inflammation marker ICAM-1 expression, monocyte adhesion, platelet binding and vascular permeability. Furthermore, we demonstrated that Puumala orthohantavirus infection causes endothelial cell activation in primary human umbilical vein endothelial cells resulting in increased monocyte adhesion without directly causing vascular permeability increases.

Conclusions

These results characterize a novel three-dimensional vessel-on-chip platform to study orthohantavirus pathogenesis. This platform can be expanded by addition of co-cultures with other (immune) cell types to optimize representation of organ-specific microenvironments. Ultimately, this platform will pave the way for studying pathogenesis or assessment of possible therapeutics for a wide range of endotheliotropic viruses.

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USUTU VIRUS: COMPARING VIRULENCE OF CIRCULATING STRAINS IN A MOUSE MODEL

Session Type
Workshop Session
Date
07/20/2022
Session Time
07:00 PM - 08:30 PM
Room
Hall 1
Presenter
  • J. M. Duyvestyn (Netherlands)
Lecture Time
07:40 PM - 07:50 PM

Abstract

Background and Aims

Knowledge of emerging infectious diseases helps us better prepare for outbreaks in changing future scenarios. Due to the emergence of vector mosquitoes the threat of arboviral diseases is increasing. Usutu is a flavivirus spreading through Europe, causing death in bird populations, but also sometimes severe infection in humans. There are currently few tools available to study this disease and little understanding of the difference in pathogenicity of different strains. We aim to better study and compare strains circulating within the Netherlands using a mouse model.

Methods

IFNAR-/- mice were injected subcutaneously with decreasing titres of Africa-3 lineage Usutu virus to determine a minimal lethal dose, or with 100pfu of three different Usutu virus lineages in order to compare virulence. Weight and survival was monitored for 16 days. Blood samples were taken, and when the animals reached a humane end point organs were harvested for pathology, immunohistochemistry and to determine viral titres by qRT-PCR.

Results

Much lower titres of virus were required in order to achieve a sublethal dose than expected. We also observed higher virulence in two of the Usutu lineages which showed more rapid disease progression and weight loss, resulting in earlier lethality. This was also evident in the earlier increase in viral titres determined from the blood samples taken during the course of infection.

Conclusions

We determined a minimal lethal dose for the Africa-3 lineage and compared the differences in virulence caused by three Usutu lineages, which will help to develop further tools and understanding to be better prepared for future outbreaks.

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PERSISTENT EXPRESSION OF HPV ONCOGENES AMONG HIV-INFECTED WOMEN ON HAART IN IBADAN NIGERIA

Session Type
Workshop Session
Date
07/20/2022
Session Time
07:00 PM - 08:30 PM
Room
Hall 1
Presenter
  • A. O. Faneye (Nigeria)
Lecture Time
07:50 PM - 08:00 PM

Abstract

Background and Aims

The natural history of HIV infection has been greatly changed by the introduction of highly active antiretroviral therapy (HAART) with a significantly improved immunity and increased life expectancy but its impact on HPV-associated cancer is uncertain. This study aims to investigates persistent HPV infection among HIV infected women on HAART by measuring the expression of HPV oncogenes over a period of 18 months after HAART initiation.

Methods

A total of 350 HIV infected women who were newly initiated on HAART in South-western Nigeria and consented to participate were enrolled in the study. Cervical swab was collected from these women and tested for HPV DNA using primers targeting the L1 gene. Total RNA was extracted from the swab and used for quantification of expression of HPV E6/7 genes relative to the actin gene on the samples that tested positive for HPV DNA using Sybr real-time. The data collected were analysed using descriptive statistics chi square and ANOVA.

Results

A prevalence of 35.6% (124) of HPV infection was observed among the 350 HIV infected women in this study. Persistent higher expression of HPV oncogenes relative to the actin gene was observed in 63.7% of the 124 women with detectable HPV DNA at the three check-point over the 18 months period.

Conclusions

Persistent active HPV infection was observed in majority of HIV infected women. Placement of HAART was observed not to have effect on the expression of the virus oncogene and persistent infection among these women.

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Live Q&A

Session Type
Workshop Session
Date
07/20/2022
Session Time
07:00 PM - 08:30 PM
Room
Hall 1
Lecture Time
08:00 PM - 08:30 PM