Hepatitis C viral infection



Pablo Gastaminza Landart

Group Leader



Research summary

Our laboratory is interested in deciphering the molecular events underlying the functional dependence of HCV infection on lipid and lipoprotein metabolism and how to exploit these pathways to inhibit HCV infection. We use a cell culture infection system based on the infectious molecular clone JFH-1 and the Huh-7 hepatoma cell line and derived subclones to evaluate the impact that genetic and pharmacological manipulation of cellular lipid metabolism has on HCV infection and pathogenesis.



Sepúlveda-Crespo D, Jiménez JL, Gómez R, De La Mata FJ, Majano PL, Muñoz-Fernández MÁ, Gastaminza P. Polyanionic carbosilane dendrimers prevent hepatitis C virus infection in cell culture. Nanomedicine 2017; 13: 49-58

Pérez-Berná AJ, Rodríguez MJ, Chichón FJ, Friesland MF, Sorrentino A, Carrascosa JL, Pereiro E, Gastaminza P. Structural Changes In Cells Imaged by Soft X-ray Cryo-Tomography During Hepatitis C Virus Infection. ACS Nano 2016; 10: 6597-611

Carnero E, Barriocanal M, Prior C, Pablo Unfried J, Segura V, Guruceaga E, Enguita M, Smerdou C, Gastaminza P, Fortes P. Long noncoding RNA EGOT negatively affects the antiviral response and favors HCV replication. EMBO Rep 2016; 17: 1013-28

Benedicto I, Gondar V, Molina-Jiménez F, García-Buey L, López-Cabrera M, Gastaminza P, Majano PL. Clathrin mediates infectious hepatitis C virus particle egress. J Virol 2015; 89: 4180-90

Vasallo C, Gastaminza P. Cellular stress responses in hepatitis C virus infection: Mastering a two-edged sword. Virus Res 2015; 209: 100-17


figuraHepatitis C virus (HCV) is a pathogen that infects 3% of the human population worldwide. Despite great efforts to control this pandemic, 3 to 4 million people become infected and about 350,000 individuals die of HCV-related diseases every year. Our laboratory is interested in the cellular and molecular processes that underlie different aspects of HCV biology and pathogenesis, to discover new targets for antiviral therapy.

Using a cell culture model of HCV infection, we identified a host factor, the sigma-1 receptor (S1R), with a specific role at the onset of the HCV lifecycle. This cell factor is an important component of mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) and regulates bidirectional interorganellar transport of lipids and Ca2+ ions between mitochondria and the ER. Silencing of this factor resulted in a proportional decrease in susceptibility to HCV infection. Mechanistic studies indicated that early steps in viral RNA replication downstream of translation of the incoming viral genomes are rate-limited by cellular S1R levels. These findings raise the possibility that HCV uses MAM as a gateway to the cell machinery necessary for efficient viral replication. We are currently determining the molecular mechanisms by which HCV uses S1R and the potential pathological consequences, using broad approaches that involve determination of alterations in the proteomic composition of S1R-containing macromolecular complexes during HCV infection.

In addition to these basic studies, we sought new molecules with antiviral potential against HCV. Using a screening system designed in-house, we interrogated a chemical library of 478 compounds approved for use in clinical practice for non-HCV applications. The rationale is that prior knowledge of the molecular mechanisms of their pharmacological action as well as their cell targets, toxicity, bioavailability and pharmacokinetics could expedite translation to the clinic. In this study, we identified a set of 12 compounds, of which two (hydroxyzine and benztropine) were selected for further characterisation. At micromolar concentrations, these compounds selectively blocked HCV entry; hydroxyzine was antiviral at clinically achievable doses, preferentially for genotype 2 viruses.






Pablo Gastaminza Landart Principal investigator
Lidia Mingorance Pérez Predoctoral scientist
Victoria Castro Illana Student

NOTE! This site uses cookies and similar technologies.

If you continue browsing or do not change browser settings, we consider your acepptance for using. Learn more

I understand


A cookie is a text file that is stored on your computer or mobile device via a web server and only that server will be able to retrieve or read the contents of the cookie and allow the Web site remember browser preferences and navigate efficiently. Cookies make the interaction between the user and the website faster and easier.

General information

This Website uses cookies. Cookies are small text files generated by the web pages you visit, which contain the session data that can be useful later in the website. In this way this Web remembers information about your visit, which can facilitate your next visit and make the website more useful.

How do cookies?

Cookies can only store text, usually always anonymous and encrypted. No personal information is ever stored in a cookie, or can be associated with identified or identifiable person.

The data allow this website to keep your information between the pages, and also to discuss how to interact with the website. Cookies are safe because they can only store information that is put there by the browser, which is information the user entered in the browser or included in the page request. You can not run the code and can not be used to access your computer. If a website encrypts cookie data, only the website can read the information.

What types of cookies used?

The cookies used by this website can be distinguished by the following criteria:

1. Types of cookies as the entity that manages:

Depending on who the entity operating the computer or domain where cookies are sent and treat the data obtained, we can distinguish:

- Own cookies: are those that are sent to the user's terminal equipment from a computer or domain managed by the editor itself and from which provides the service requested by the user.

- Third party cookies: these are those that are sent to the user's terminal equipment from a machine or domain that is not managed by the publisher, but by another entity data is obtained through cookies.

In the event that the cookies are installed from a computer or domain managed by the editor itself but the information collected by these is managed by a third party can not be considered as party cookies.

2. Types of cookies as the length of time that remain active:

Depending on the length of time that remain active in the terminal equipment can be distinguished:

- Session cookies: cookies are a type designed to collect and store data while the user accesses a web page. Are usually used to store information that only worth preserving for the service requested by the user at any one time (eg a list of products purchased).

- Persistent cookies: cookies are a type of data which are stored in the terminal and can be accessed and treated for a period defined by the head of the cookie, and can range from a few minutes to several years.

3. Cookies types according to their purpose:

Depending on the purpose for which the data are processed through cookies, we can distinguish between:

- Technical cookies: these are those that allow the user to navigate through a web page or application platform and the use of different options or services it exist as, for example, control traffic and data communication, identify the session, access to restricted access parts, remember the elements of an order, make the buying process an order, make an application for registration or participation in an event, use security features while browsing store content for dissemination videos or sound or share content via social networks.

- Customization cookies: these are those that allow the user to access the service with some general characteristics based on a predefined set of criteria in the user terminal would eg language, the type of browser through which you access the service, the locale from which you access the service, etc.

- Analysis cookies: they are those that allow the responsible for them, monitoring and analyzing the behavior of users of the web sites that are linked. The information gathered through such cookies are used in measuring the activity of web sites, application or platform and for the profiling of user navigation of such sites, applications and platforms, in order to make improvements function data analysis how users use the service.

Management tool cookies

This Website uses Google Analytics.

Google Analytics is a free tool from Google that primarily allows website owners know how users interact with your website. Also, enable cookies in the domain of the site in which you are and uses a set of cookies called "__utma" and "__utmz" to collect information anonymously and reporting of website trends without identifying individual users..

For statistics of use of this website use cookies in order to know the level of recurrence of our visitors and more interesting content. This way we can concentrate our efforts on improving the most visited areas and make the user more easily find what they are looking for. On this site you can use the information from your visit for statistical evaluations and calculations anonymous data and to ensure the continuity of service or to make improvements to their websites. For more details, see the link below privacy policy [http://www.google.com/intl/en/policies/privacy/]

How to manage cookies on your computer: disabling and deleting cookies

All Internet browsers allow you to limit the behavior of a cookie or disable cookies within settings or browser settings. The steps for doing so are different for each browser, you can find instructions in the help menu of your browser.

If you decline the use of cookies, since it is possible thanks to the preferences menu of your browser or settings, reject, this website will continue to function properly without the use of the same.

Can you allow, block or delete cookies installed on your computer by setting your browser options installed on your computer:

- For more information about Internet Explorer click here.
- For more information on Chrome click here.
- For more information about Safari click here.
- For more information about Firefox click here.

Through your browser, you can also view the cookies that are on your computer, and delete them as you see fit. Cookies are text files, you can open and read the contents. The data within them is almost always encrypted with a numeric key corresponding to an Internet session so often has no meaning beyond the website who wrote it.

Informed consent

The use of this website on the other hand, implies that you paid your specific consent to the use of cookies, on the terms and conditions provided in this Cookies Policy, without prejudice to the measures of deactivation and removal of cookies that you can take, and mentioned in the previous section.