T3S-1124 - UMR-S 1124
Université de Paris
Campus Saint-Germain-des-Près
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
- T cell apoptosis characterizes severe Covid-19 disease.
André S, Picard M, Cezar R, Roux-Dalvai F, Alleaume-Butaux A, Soundaramourty C, Cruz AS, Mendes-Frias A, Gotti C, Leclercq M, Nicolas A, Tauzin A, Carvalho A, Capela C, Pedrosa J, Castro AG, Kundura L, Loubet P, Sotto A, Muller L, Lefrant JY, Roger C, Claret PG, Duvnjak S, Tran TA, Racine G, Zghidi-Abouzid O, Nioche P, Silvestre R, Droit A, Mammano F, Corbeau P, Estaquier J : Cell Death Differ, 2022 - Differential Inhibition of HIV Replication by the 12 Interferon Alpha Subtypes.
Tauzin A, Espinosa Ortiz A, Blake O, Soundaramourty C, Joly-Beauparlant C, Nicolas A, Droit A, Dutrieux J, Estaquier J, Mammano F : J Virol, 2021 - Early Antiretroviral Therapy Prevents Viral Infection of Monocytes and Inflammation in Simian Immunodeficiency Virus-Infected Rhesus Macaques.
Rabezanahary H, Clain J, Racine G, Andreani G, Benmadid-Laktout G, Borde C, Mammano F, Mesplèdes T, Ancuta P, Zghidi-Abouzid O, Estaquier J : J Virol, 2020 - Detection of pretreatment minority HIV-1 reverse transcriptase inhibitor-resistant variants by ultra-deep sequencing has a limited impact on virological outcomes.
Su B, Zheng X, Liu Y, Liu L, Xin R, Lu H, Huang C, Bai L, Mammano F, Zhang T, Wu H, Sun L, Dai L : J Antimicrob Chemother, 2019 - Genetically Intact but Functionally Impaired HIV-1 Env Glycoproteins in the T-Cell Reservoir.
de Verneuil A, Migraine J, Mammano F, Molina JM, Gallien S, Mouquet H, Hance AJ, Clavel F, Dutrieux J : J Virol, 2018 - Dynamics of HIV-1 coinfection in different susceptible target cell populations during cell-free infection.
Ito Y, Tauzin A, Remion A, Ejima K, Mammano F, Iwami S : J Theor Biol, 2018 - Genetic and phenotypic analyses of sequential vpu alleles from HIV-infected IFN-treated patients.
Vanwalscappel B, Rato S, Perez-Olmeda M, Díez Fuertes F, Casartelli N, Alcami J, Mammano F : Virology, 2017 - Single-dose pharmacokinetics and pharmacodynamics of oral tenofovir and emtricitabine in blood, saliva and rectal tissue: a sub-study of the ANRS IPERGAY trial.
Fonsart J, Saragosti S, Taouk M, Peytavin G, Bushman L, Charreau I, Hance A, Goldwirt L, Morel S, Mammano F, Loze B, Capitant C, Clavel F, Mahjoub N, Meyer L, Anderson PL, Delaugerre C, Molina JM : J Antimicrob Chemother, 2017 - Number of infection events per cell during HIV-1 cell-free infection.
Ito Y, Remion A, Tauzin A, Ejima K, Nakaoka S, Iwasa Y, Iwami S, Mammano F : Sci Rep, 2017 - Kinetics of the establishment of HIV-1 viral interference and comprehensive analysis of the contribution of viral genes.
Remion A, Delord M, Hance AJ, Saragosti S, Mammano F : Virology, 2016 - CIB1 and CIB2 are HIV-1 helper factors involved in viral entry.
Godinho-Santos A, Hance AJ, Gonçalves J, Mammano F : Sci Rep, 2016 - Impact of the HIV integrase genetic context on the phenotypic expression and in vivo emergence of raltegravir resistance mutations.
Nguyen TT, Rato S, Molina JM, Clavel F, Delaugerre C, Mammano F : J Antimicrob Chemother, 2015 - Quantifying the Antiviral Effect of IFN on HIV-1 Replication in Cell Culture.
Ikeda H, Godinho-Santos A, Rato S, Vanwalscappel B, Clavel F, Aihara K, Iwami S, Mammano F : Sci Rep, 2015 - Cell-to-cell infection by HIV contributes over half of virus infection.
Iwami S, Takeuchi JS, Nakaoka S, Mammano F, Clavel F, Inaba H, Kobayashi T, Misawa N, Aihara K, Koyanagi Y, Sato K : Elife, 2015 - HIV cell-to-cell transmission requires the production of infectious virus particles and does not proceed through env-mediated fusion pores.
Monel B, Beaumont E, Vendrame D, Schwartz O, Brand D, Mammano F : J Virol, 2012 - Hyperthermia stimulates HIV-1 replication.
Roesch F, Meziane O, Kula A, Nisole S, Porrot F, Anderson I, Mammano F, Fassati A, Marcello A, Benkirane M, Schwartz O : PLoS Pathog, 2012