Wednesday, 29th January 2020

Virology and Microbiology

  Human immunodeficiency virus reverse transcriptase and antiretroviral therapy



 2016 06 17 Grupo Luis Menendez 11 400px


Luis Menéndez-Arias








Research summary

The human immunodeficiency virus (HIV) is a retrovirus that infects cells of the immune system, and is the etiological agent of AIDS. Nowadays, treatment of HIV-infection involves the use of inhibitors of retroviral enzymes such as the reverse transcriptase (RT), protease and integrase; as well as drugs targeting viral entry. Combination therapies including two or three RT inhibitors have been rather successful in the clinic, and play a key role in the management of HIV-infected individuals. However, the emergence of resistant viruses, the observed cross-reactivity between the inhibitors, and unwanted secondary effects are major hurdles towards their long-term efficacy.

We are interested in therapeutic targets for HIV, emphasizing on the role of the viral RT. HIV RT plays a pivotal role in the replication of the viral genomic RNA. Recently, our efforts have been directed towards two major goals: (1) understanding the role of different amino acids in the nucleotide specificity of the enzyme, as well as in its fidelity of DNA synthesis; and (2) the elucidation of molecular mechanisms involved in RT inhibitor resistance and the analysis of the contribution of different amino acid substitutions in the acquisition of drug resistance.

Nucleotide specificity studies are relevant in drug resistance but are also important to develop useful tools in molecular biology. Thus, we are trying to obtain more stable and faithful RTs, with biotechnological applications (for example, in the analysis of gene expression). Understanding the role of different residues in RT function (both on DNA polymerase activity, but also in modulating RNase H function and reverse transcription initiation) should help us to design novel strategies for treating HIV infection.

Fig1 300px


 . ................

Fig2 300px
Amino acid residues in the HIV-1 RT thumb-connection subdomains and the RNase H domain can modulate resistance to AZT and other nucleoside inhibitors by altering the balance between excision and template RNA degradation (Menéndez-Arias, 2013; Antiviral Res. 98, 93).         RT-PCR assays showing the effect of the temperature on the cDNA synthesis catalyzed by engineered recombinant HIV-1 group O RT variants (Matamoros et al. 2013; Biochemistry 52, 9318).


Relevant publications:

  • Barrioluengo, V., Álvarez, M., Barbieri, D., Menéndez-Arias, L. (2011) Thermostable HIV-1 group O reverse transcriptase variants with the same fidelity as murine leukaemia virus reverse transcriptase. Biochem. J. 436, 599-607
  • Kisic, M., Matamoros, T., Nevot, M., Mendieta, J., Martinez-Picado, J., Martínez, M.A., Menéndez-Arias, L. (2011) Thymidine analogue excision and discrimination modulated by mutational complexes including single amino acid deletions of Asp-67 or Thr-69 in HIV-1 reverse transcriptase. J. Biol. Chem. 286, 20615-20624
  • Betancor, G., Garriga, C., Puertas, M.C., Nevot, M., Anta, L., Blanco, J.L., Pérez-Elías, M.J., de Mendoza, C., Martínez, M.A., Martinez-Picado, J., Menéndez-Arias, L., for the Resistance Platform of the Spanish AIDS Research Network (ResRIS) (2012) Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy. Retrovirology 9, 68. 
  • Álvarez, M., Barrioluengo, V., Afonso-Lehmann, R., Menéndez-Arias, L. (2013) Altered error specificity of RNase H-deficient HIV-1 reverse transcriptases during DNA-dependent DNA synthesis. Nucleic Acids Res. 41, 4601-4612.   
  • Betancor, G., Álvarez, M., Marcelli, B., Andrés, C., Martínez, M.A., Menéndez-Arias, L. (2015) Effects of HIV-1 reverse transcriptase connection subdomain mutations on polypurine tract removal and initiation of (+)-strand DNA synthesis. Nucleic Acids Res. 43, 2259-2270.

NOTE! This site uses cookies and similar technologies.

If you not change browser settings, you agree to it. Learn more

I understand


What are cookies?

A cookie is a file that is downloaded to your computer when you access certain web pages. Cookies allow a web page, among other things, to store and retrieve information about the browsing habits of a user or their equipment and, depending on the information they contain and the way they use their equipment, they can be used to recognize the user.

Types of cookies

Classification of cookies is made according to a series of categories. However, it is necessary to take into account that the same cookie can be included in more than one category.

  1. Cookies according to the entity that manages them

    Depending on the entity that manages the computer or domain from which the cookies are sent and treat the data obtained, we can distinguish:

    • Own cookies: those that are sent to the user's terminal equipment from a computer or domain managed by the editor itself and from which the service requested by the user is provided.
    • Third party cookies: those that are sent to the user's terminal equipment from a computer or domain that is not managed by the publisher, but by another entity that processes the data obtained through the cookies. When cookies are installed from a computer or domain managed by the publisher itself, but the information collected through them is managed by a third party, they cannot be considered as own cookies.

  2. Cookies according to the period of time they remain activated

    Depending on the length of time that they remain activated in the terminal equipment, we can distinguish:

    • Session cookies: type of cookies designed to collect and store data while the user accesses a web page. They are usually used to store information that only is kept to provide the service requested by the user on a single occasion (e.g. a list of products purchased).
    • Persistent cookies: type of cookies in which the data is still stored in the terminal and can be accessed and processed during a period defined by the person responsible for the cookie, which can range from a few minutes to several years.

  3. Cookies according to their purpose

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

    • Technical cookies: those that allow the user to navigate through a web page, platform or application and the use of different options or services that exist in it, such as controlling traffic and data communication, identifying the session, access to restricted access parts, remember the elements that make up an order, perform the purchase process of an order, make a registration or participation in an event, use security elements during navigation, store content for the broadcast videos or sound or share content through social networks.
    • Personalization cookies: those that allow the user to access the service with some predefined general characteristics based on a series of criteria in the user's terminal, such as the language, the type of browser through which the user accesses the service, the regional configuration from where you access the service, etc.
    • Analytical cookies: those that allow the person responsible for them to monitor and analyse the behaviour of the users of the websites to which they are linked. The information collected through this type of cookies is used in the measurement of the activity of the websites, applications or platforms, and for the elaboration of navigation profiles of the users of said sites, applications and platforms, in order to introduce improvements in the analysis of the data of use made by the users of the service.

Cookies used on our website

The CBMSO website uses Google Analytics. Google Analytics is a simple and easy to use tool that helps website owners to measure how users interact with the content of the site. You can consult more information about the cookies used by Google Analitycs in this link.

Acceptance of the Cookies Policy

The CBMSO assumes that you accept the use of cookies if you continue browsing, considering that it is a conscious and positive action from which the user's consent is inferred. In this regard, you are previously informed that such behaviour will be interpreted that you accept the installation and use of cookies.

Knowing this information, it is possible to carry out the following actions:

How to modify the configuration of cookies

Using your browser you can restrict, block or delete cookies from any web page. In each browser the process is different, here we show you links on this particular of the most used browsers: