Fabrizio MAMMANO

T3S-1124 - UMR-S 1124
Université Paris Descartes
45 rue des Saints Pères
75270 Paris Cedex 06

Fax : +33 (0) 1 42 86 38 68

Dr. Fabrizio MAMMANO

INSERM researcher, DR- INSERM
Cell death in host-pathogen interactions

fabrizio.mammano@-Code to remove to avoid SPAM-inserm.fr

Our laboratory explores different aspects of Human Immunodeficiency Virus (HIV) replication, evolution and pathogenesis. Our approach aims a better understanding of the virus replication and escape pathways to conceive appropriate antiviral strategies (“know your enemy”). To this end, we study patient-derived viral variants, using molecular and cellular approaches, to elucidate their role in viral pathogenesis and their response to treatment. The main research axes are described in the section here below.

In 2019, we joined the research group “Cell death in host-pathogen interaction”, whose complementary expertise covers apoptosis, inflammation and cellular metabolism. Our laboratory is located in the Centre Universitaire des Saints Pères. We are affiliated with Université de Paris, and the doctoral school Bio-SPC (Sorbonne Paris Cité).

CURRENT RESEARCH AXES

1)  HIV reservoirs in treated patients

One of the major hurdles to HIV eradication is the early establishment of viral reservoirs in infected patients. Viral reservoirs consist of cells carrying a stably integrated, latent, HIV genome, whose expression can be reactivated. Different strategies aimed at accelerating the clearance of the latent reservoir are currently undergoing clinical trials. A central question for the design of such studies is to characterize the replication competent viral variants present in the reservoirs. By using complementary technologies, including a quantitative virus outgrowth assay (qVOA), we explore the initial seeding of the reservoirs in newly infected patients and the genotypic and phenotypic characteristics of viral variants persisting in reservoir of successfully treated patients.

2)  HIV inhibition by IFN and viral escape

Type-I interferons (IFN) are known to inhibit both early and late steps of HIV-1 replication in vitro, by inducing the expression of several proteins endowed with antiviral properties. We have initially measured the potency of IFN inhibition in tissue culture using experimental approaches followed by mathematical modeling, in collaboration with Prof. Shingo Iwami (Kyushu, Japan). We are currently exploring differences in the antiviral activities of individual IFN-alpha subtypes. In parallel, we study virus escape strategies both in experimental systems and in IFN-treated patients. In vivo, in collaboration with the team of Prof. Jose Alcami (Madrid, Spain), we have described changes in the composition of HIV populations over-time. The characterization of the phenotypic properties of emerging viral variants is a major focus of our research.

3)  HIV-induced resistance to super-infection

Viral interference is a phenomenon by which a virus-infected cell displays reduced susceptibility to a second infection. Double-infections, however, allows genetic recombination, contributing to HIV diversity, evolution, and pathogenesis. Thus, while HIV can clearly induce interference under some circumstances, the kinetics of this phenomenon appear to be regulated. Recent work from our group has identified a key viral gene responsible for potent early interference. The characterization of the mechanism is under investigation.

COLLABORATIONS

Prof Shingo IWAMI

University of Kyushu, JAPAN

Mathematic modeling of HIV replication, transmission and inhibition

http://bio-math10.biology.kyushu-u.ac.jp/english/member/iwami.html

Prof José ALCAMI

Instituto de Salud Carlo III, Madrid, SPAIN

HIV evolution in IFN-treated patients

http://www.hiv-lab.com/index.php/the-lab/alcami

Prof Joao GONCALVES

University of Lisbon, PORTUGAL

Virus replication, antiviral strategies

http://imed.ulisboa.pt/cv/joao-manuel-braz-goncalves/

Recent Publications

Articles