Study of Vaccinia Virus Interactions with the Host and Reactivation of the Latent HIV-1

Study of Vaccinia Virus Interactions with the Host and Reactivation of the Latent HIV-1

MUDr. Zora Mělková, Ph.D.

MUDr. Zora Mělková, Ph.D. — Project head

About us

The main focus of the project consists in the studies of interactions of vacccinia virus and HIV-1 with the host; specifically responses of the atopic organism towards infection with vaccinia virus and the effect of redox potential on reactivation of the latent HIV-1 will be studied. The research should provide a basis for new therapeutic and vaccination approaches usable in infections with these viruses.

Research Objectives:

  • To develop a mouse model of eczema vaccinatum in Nc/Nga mice or in a different mouse model of atopic dermatitis, and to study immune responses of the atopic organism to vaccinia virus.
  • To test the antiviral effect of selected derivatives of the ethacrynic acid and other agents with the anti-poxviral effect in vivo; in tissue culture, to study the exact mechanism of action of the agents, the type of cell death of the infected cells of different embryonic origin and its significance for induction of the immune responses in infection with vaccinia virus
  • To characterize the molecular mechanism of action of redox-modulating agents on reactivation of the latent HIV-1 and to verify the results obtained in vitro in tissue cultures also in primary peripheral lymphocytes of healthy donors and HIV+ patients ex vivo.

Further information can be found at www.phenogenomics.cz or at the link https://biocev.lf1.cuni.cz/

 

Content of the research:

Our primary research focus is to study virus-host interactions, namely interactions between vaccinia virus and HIV-1. The research should provide the basis for new therapeutic and vaccination approaches usable in infections with these and other viruses.

Contrary to a common belief, the need to understand pathogenesis of poxvirus infection and post-vaccination complications as well as to develop safe vaccination vectors and/or drugs effective against poxviruses still remains. The main focus of our research is the response of an atopic organism towards vaccinia and other viruses. We have developed our own model of eczema vaccinatum in atopic Nc/Nga mice, used it to characterize immune responses and to compare the risks and efficiencies of vaccinations with vaccinia virus strain WR, Dryvax and non-replicating MVA. In this atopic model, we continue to study the disregulated immune responses towards vaccinia and other viruses.

HIV latency in reservoir cells is the main obstacle to cure HIV/AIDS. Our goal is to identify, characterize and develop new agents to reactivate latent HIV-1. We have described a reactivation potential of heme arginate and we identified several other HIV-1-reactivating agents in vitro in tissue cultures. We are currently focusing on confirmation of the results in primary peripheral lymphocytes of HIV + patients and in primary latency models. We intend to patient selected drug combinations and to seek for a strategic partner to further develop the new HIV treatment.

 

Potential for Cooperation

We are open to new PhD students and to any type of collaboration/exchange with researchers interested in studying the immune responses of an atopic organism towards vaccinia and other viruses. To further develop new agents effective a reactivation of latent HIV, we are seeking for a strategic investor.

Publications

2017

Shankaran P, Madlenakova M, Hajkova V, Jilich D, Svobodova I, Horinek A, Fujikura Y, Melkova Z. Effects of Heme degradation products on reactivation of latent HIV-1. Acta Virol. 2017 Feb 6;61(1). doi: 10.4149/av_2017_01_86. (IF 1.222)

Melkova Z, Shankaran P, Madlenakova M, Bodor J. Current views on HIV-1 latency, persistence, and cure. Folia Microbiol (Praha). 2017 Jan;62(1):73-87. doi: 10.1007/s12223-016-0474-7. (IF 1.335)

2016

Fujikura Y, Krijt J, Povýšil C, Mělková Z, Přikryl P, Vokurka M, Nečas E. Iron Overload Causes Alterations of E-Cadherin in the Liver. Folia Biol (Praha). 2016;62(3):95-102. PubMed PMID: 27516188. (IF 0.833)

Team

MUDr. Zora Mělková, Ph.D.

MUDr.
Zora Mělková, Ph.D.

Head of Group Study of Vaccinia Virus Interactions with the Host and Reactivation of the Latent HIV-1

zora.melkova@lf1.cuni.cz
+420325873014, +420325873006