UMR 941 – Equipe 1 - Evolution et pathogenèses virales
We are interested in different aspects of Human Immunodeficiency Virus (HIV) replication, evolution and pathogenesis. The main research axes are described here below. In our group, researchers interested in molecular and cellular virology work together with clinical investigators focused on virus pathogenesis and treatment strategies. Research facilities are located within the IUH (Institut Universitaire d’Hématologie), and at the Hospital (Clinical Infectious Disease Department, and Microbiology Department).
Thèmes de recherche
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 how to measure the impact of the treatment on the latent reservoir. Different approaches were developed, based on DNA measurement or viral outgrowth assays, each of which has specific advantages and drawbacks. By using different technologies, we aim at exploring the initial seeding of the reservoir in newly infected patients and the properties of viral variants whose expression can be induced from resting cells of the reservoir by appropriate stimulations.
2- HIV evolution under the selective pressure of IFN in treated patients
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 potential virus escape strategies both in experimental systems and in IFN-treated patients. In vivo, changes in the composition of HIV populations over-time were analyzed by deep-sequencing in collaboration with the team of Prof. Jose Alcami (Madrid, Spain). The characterization of the phenotypic properties of emerging viral variants is a major focus of our research.
3- HIV-induced resistance to super-infection: kinetics and viral factors involved
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, this phenomenon appears 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.
Equipes de recherche
Our research team consists of a group of experimental researchers who apply molecular and cell-biology approaches to study HIV replication and evolution, and a group of medical virologists conducting clinically-oriented research on HIV prevention, treatment and pathogenesis.
Fabrizio MAMMANO, DR-2 Inserm
Alexandra TAUZIN, PhD Student (BioSPC, Paris Diderot)
Alexandre NICOLAS, Master Student (IMVI, Paris Diderot)
Julie MIGRAINE, Assistant Engineer, Inserm (50%)
Constance DELAUGERRE, Professor, PU-PH (Univ. Paris 7)
Jean-Michel MOLINA, Professor, PU-PH (Univ. Paris 7)
Marie-Laure CHAIX, MCU-PH (Univ. Paris 7)
Héloïse DELAGREVERIE, Master Student (Univ. Paris 7)
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.
Journal of Virology, 2012, PMID: 22258237
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.
Journal of Antimicrobial Chemotherapy, 2014, PMID: 25336162
Archived HIV-1 DNA resistance mutations to rilpivirine and etravirine in successfully treated HIV-1-infected individuals pre-exposed to efavirenz or nevirapine.
Gallien S, Charreau I, Nere ML, Mahjoub N, Simon F, de Castro N, Aboulker JP, Molina JM, Delaugerre C
Journal of Antimicrobial Chemotherapy, 2014
Safety and efficacy of coformulated efavirenz/emtricitabine/tenofovir single-tablet regimen in treatment-naive patients infected with HIV-1.
Gallien S, Flandre P, Nguyen N, De Castro N, Molina JM, Delaugerre C.
Journal of Medical Virology, 2014, PMID: 25070158
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.
Scientific Reports (Nature Publishing Group), 2015, PMID: 26119462
Cell-to-cell infection by HIV contributes over half of virus infection.
Iwami S., Takeuchi J.S., Nakaoka S., Mammano F., Clavel F., Inaba H., Kobayashi T., Misawa N., Aihara K., Koyanagi Y., Sato K.
eLife, 2015, (PMID: 26441404)
On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection.
Molina JM1, Capitant C, Spire B, Pialoux G, Cotte L, Charreau I, Tremblay C, Le Gall JM, Cua E, Pasquet A, Raffi F, Pintado C, Chidiac C, Chas J, Charbonneau P, Delaugerre C, Suzan-Monti M, Loze B, Fonsart J, Peytavin G, Cheret A, Timsit J, Girard G, Lorente N, Préau M, Rooney JF, Wainberg MA, Thompson D, Rozenbaum W, Doré V, Marchand L, Simon MC, Etien N, Aboulker JP, Meyer L, Delfraissy JF; ANRS IPERGAY Study Group.
The New England Journal of Medicine. 2015 PMID:26624850
Remion A., Delord M., Hance A.J., Saragosti S., Mammano F.
Kinetics of the establishment of HIV-1 viral interference and comprehensive analysis of the contribution of viral genes.
Virology, 2016; 487: 59-67 (PMID: 26499042).
Godinho-Santos A., Hance A.J., Gonçalves J., Mammano F.
CIB1 and CIB2 are HIV-1 helper factors involved in viral entry.
Scientific Reports (Nature Publishing Group), 2016; 6:30927 (PMID: 27489023).
Vanwalscappel B., Rato S., Perez-Olmeda M., Diez-Fuertez F., Casartelli N., Alcami J., Mammano F.
Genetic and phenotypic analyses of sequential vpu alleles from HIV-infected IFN-treated patients.
Virology, 2017; 500: 247-258 (PMID: 27855354).