Our research integrates diverse techniques and approaches from cell culture, virology, molecular biology, biochemistry and bioinformatics to uncover novel innate inhibitors and dependency factors of HIV, Influenza, SARS-CoV-2, and other viruses. We also seek to understand these host factors’ mechanism of action at the cellular and molecular levels. Identifying host-viral interactions and molecular mechanisms involved permits to clarify principles that explain viral infection, replication and spread.
The balance between dependency and restriction host factors dictate cell permissivity and thus transgene expression. This knowledge will then be applied to the optimisation of vectors for gene therapy and regenerative medicine.
People
Themes

Uncovering novel host factors that regulate HIV-1
We are studying natural human variation to further understand and discover new host regulators of HIV-1 infection and replication. Subtle differences in the human population have been captured in an extensively characterised library of induced Pluripotent Stem Cells (www.hipsci.org). These cell lines display different infection phenotypes. Correlating genotypes that explain the observed extreme phenotypes in a systems approach will permit to identify HIV-1 host regulatory factor candidates. These we will then be validated and further studied in vitro models.

Development of lentiviral vectors to target specific cells in vivo
We will use the breadth of knowledge generated in HIV research and particularly within our department to develop lentiviral vectors that target specific cells in vivo. This may revolutionise the paradigm of gene and cell therapy: current medicines are highly costly which involve patient target cell isolation, correction of genetic mutations or addition of a new/repaired gene, and reintroduction of the altered cells into the patient. In vivo gene therapy would be a cheaper process, with a single-dose medicine that could be used for many patients. We are currently developing vectors that can specifically target T cells. This will allow the genetic modification of T cells to express chimeric antigen receptors (CAR-T Cells) and ultimately their use in cancer treatment.
Publications
The old and the new: Prospects for non-integrating lentiviral vector technology
Apolonia, L., Oct 2020, In: Viruses. 12, 10, 1103.Research output: Contribution to journal › Review article › peer-review
The GTPase Domain of MX2 Interacts with the HIV-1 Capsid, Enabling Its Short Isoform to Moderate Antiviral Restriction
Betancor , G., Dicks, M. D. J., Jimenez Guardeno, J. M., Ali, N. H., Apolonia, L. & Malim, M. H., 12 Nov 2019, In: Cell Reports. 29, 7, p. 1923-1933.e3Research output: Contribution to journal › Article › peer-review
Immunoproteasome activation enables human TRIM5α restriction of HIV-1
Jimenez Guardeno, J. M., Apolonia, L. F. S., Betancor Quintana, G. J. & Malim, M., 1 Jun 2019, In: Nature Microbiology. 4, 6, p. 933-940 8 p.Research output: Contribution to journal › Letter › peer-review
Multiple components of the nuclear pore complex interact with the amino-terminus of MX2 to facilitate HIV-1 restriction
Dicks, M. D. J., Betancor, G., Jimenez-Guardeno, J. M., Pessel-Vivares, L., Apolonia, L., Goujon, C. & Malim, M. H., 29 Nov 2018, In: PLoS Pathogens. 14, 11, e1007408.Research output: Contribution to journal › Article › peer-review
The interferon inducible isoform of NCOA7 inhibits endosome-mediated viral entry
Doyle, T., Moncorgé, O., Bonaventure, B., Pollpeter, D., Lussignol, M., Tauziet, M., Apolonia, L., Catanese, M. T., Goujon, C. & Malim, M., 1 Dec 2018, In: Nature Microbiology. 3, 12, p. 1369–1376Research output: Contribution to journal › Article › peer-review
Heteromeric interactions regulate butyrophilin (BTN) and BTN-like molecules governing γδ T cell biology
Vantourout, P., Laing, A., Woodward, M. J., Zlatareva, I., Apolonia, L., Jones, A. W., Snijders, A. P., Malim, M. H. & Hayday, A. C., 30 Jan 2018, In: Proceedings of the National Academy of Sciences of the United States of America. 115, 5, p. 1039-1044 6 p.Research output: Contribution to journal › Article › peer-review
Deep sequencing of HIV-1 reverse transcripts reveals the multifaceted antiviral functions of APOBEC3G
Pollpeter, D., Parsons, M., Sobala, A., Coxhead, S., Lang, R. D., Bruns, A. M., Papaioannou, S., McDonnell, J. M., Apolonia, L., Chowdhury, J. A., Horvath, C. M. & Malim, M., 1 Feb 2018, In: Nature Microbiology. 3, 2, p. 220-233 14 p.Research output: Contribution to journal › Article › peer-review
Effects of inner nuclear membrane proteins SUN1/UNC-84A and SUN2/UNC- 84B on the early steps of HIV-1 infection
Schaller, T., Bulli, L., Pollpeter, D., Betancor, G., Kutzner, J., Apolonia, L., Herold, N., Burk, R. & Malim, M. H., 1 Oct 2017, In: Journal of Virology. 91, 19, e00463-17.Research output: Contribution to journal › Article › peer-review
Complex interplay between HIV-1 capsid and MX2-independent alpha interferon-induced antiviral factors
Bulli, L., Apolonia, L., Kutzner, J., Pollpeter, D., Goujon, C., Herold, N., Schwarz, S. M., Giernat, Y., Keppler, O. T., Malim, M. H. & Schaller, T., 8 Jun 2016, In: Journal of Virology. 90, 16, p. 7469-7480 12 p.Research output: Contribution to journal › Article › peer-review
Oligomerization requirements for MX2 mediated suppression of HIV-1 infection
Dicks, M. D. J., Goujon, C., Pollpeter, D., Betancor, G., Apolonia, L., Bergeron, J. & Malim, M. H., Jan 2016, In: Journal of Virology. 90, 1, p. 22-32 11 p.Research output: Contribution to journal › Article › peer-review
Promiscuous RNA Binding Ensures Effective Encapsidation of APOBEC3 Proteins by HIV-1
Apolonia, L., Schulz, R., Curk, T., Rocha, P., Swanson, C. M., Schaller, T., Ule, J. & Malim, M. H., 15 Jan 2015, In: PL o S Pathogens. 11, 1, p. 1-22 22 p., e1004609.Research output: Contribution to journal › Article › peer-review
Immune evasion activities of accessory proteins Vpu, Nef and Vif are conserved in acute and chronic HIV-1 infection
Mlcochova, P., Apolonia, L., Kluge, S. F., Sridharan, A., Kirchhoff, F., Malim, M. H., Sauter, D. & Gupta, R. K., 30 Mar 2015, In: Virology. 482, p. 72-78 7 p.Research output: Contribution to journal › Article › peer-review
Nuclear import of SAMHD1 is mediated by a classical karyopherin alpha/beta 1 dependent pathway and confers sensitivity to Vpx(MAC) induced ubiquitination and proteasomal degradation
Schaller, T., Pollpeter, D., Apolonia, L., Goujon, C. & Malim, M. H., 8 Apr 2014, In: Retrovirology. 11, 16 p., 29.Research output: Contribution to journal › Article › peer-review
PhD Students
People
Themes

Uncovering novel host factors that regulate HIV-1
We are studying natural human variation to further understand and discover new host regulators of HIV-1 infection and replication. Subtle differences in the human population have been captured in an extensively characterised library of induced Pluripotent Stem Cells (www.hipsci.org). These cell lines display different infection phenotypes. Correlating genotypes that explain the observed extreme phenotypes in a systems approach will permit to identify HIV-1 host regulatory factor candidates. These we will then be validated and further studied in vitro models.

Development of lentiviral vectors to target specific cells in vivo
We will use the breadth of knowledge generated in HIV research and particularly within our department to develop lentiviral vectors that target specific cells in vivo. This may revolutionise the paradigm of gene and cell therapy: current medicines are highly costly which involve patient target cell isolation, correction of genetic mutations or addition of a new/repaired gene, and reintroduction of the altered cells into the patient. In vivo gene therapy would be a cheaper process, with a single-dose medicine that could be used for many patients. We are currently developing vectors that can specifically target T cells. This will allow the genetic modification of T cells to express chimeric antigen receptors (CAR-T Cells) and ultimately their use in cancer treatment.
Publications
The old and the new: Prospects for non-integrating lentiviral vector technology
Apolonia, L., Oct 2020, In: Viruses. 12, 10, 1103.Research output: Contribution to journal › Review article › peer-review
The GTPase Domain of MX2 Interacts with the HIV-1 Capsid, Enabling Its Short Isoform to Moderate Antiviral Restriction
Betancor , G., Dicks, M. D. J., Jimenez Guardeno, J. M., Ali, N. H., Apolonia, L. & Malim, M. H., 12 Nov 2019, In: Cell Reports. 29, 7, p. 1923-1933.e3Research output: Contribution to journal › Article › peer-review
Immunoproteasome activation enables human TRIM5α restriction of HIV-1
Jimenez Guardeno, J. M., Apolonia, L. F. S., Betancor Quintana, G. J. & Malim, M., 1 Jun 2019, In: Nature Microbiology. 4, 6, p. 933-940 8 p.Research output: Contribution to journal › Letter › peer-review
Multiple components of the nuclear pore complex interact with the amino-terminus of MX2 to facilitate HIV-1 restriction
Dicks, M. D. J., Betancor, G., Jimenez-Guardeno, J. M., Pessel-Vivares, L., Apolonia, L., Goujon, C. & Malim, M. H., 29 Nov 2018, In: PLoS Pathogens. 14, 11, e1007408.Research output: Contribution to journal › Article › peer-review
The interferon inducible isoform of NCOA7 inhibits endosome-mediated viral entry
Doyle, T., Moncorgé, O., Bonaventure, B., Pollpeter, D., Lussignol, M., Tauziet, M., Apolonia, L., Catanese, M. T., Goujon, C. & Malim, M., 1 Dec 2018, In: Nature Microbiology. 3, 12, p. 1369–1376Research output: Contribution to journal › Article › peer-review
Heteromeric interactions regulate butyrophilin (BTN) and BTN-like molecules governing γδ T cell biology
Vantourout, P., Laing, A., Woodward, M. J., Zlatareva, I., Apolonia, L., Jones, A. W., Snijders, A. P., Malim, M. H. & Hayday, A. C., 30 Jan 2018, In: Proceedings of the National Academy of Sciences of the United States of America. 115, 5, p. 1039-1044 6 p.Research output: Contribution to journal › Article › peer-review
Deep sequencing of HIV-1 reverse transcripts reveals the multifaceted antiviral functions of APOBEC3G
Pollpeter, D., Parsons, M., Sobala, A., Coxhead, S., Lang, R. D., Bruns, A. M., Papaioannou, S., McDonnell, J. M., Apolonia, L., Chowdhury, J. A., Horvath, C. M. & Malim, M., 1 Feb 2018, In: Nature Microbiology. 3, 2, p. 220-233 14 p.Research output: Contribution to journal › Article › peer-review
Effects of inner nuclear membrane proteins SUN1/UNC-84A and SUN2/UNC- 84B on the early steps of HIV-1 infection
Schaller, T., Bulli, L., Pollpeter, D., Betancor, G., Kutzner, J., Apolonia, L., Herold, N., Burk, R. & Malim, M. H., 1 Oct 2017, In: Journal of Virology. 91, 19, e00463-17.Research output: Contribution to journal › Article › peer-review
Complex interplay between HIV-1 capsid and MX2-independent alpha interferon-induced antiviral factors
Bulli, L., Apolonia, L., Kutzner, J., Pollpeter, D., Goujon, C., Herold, N., Schwarz, S. M., Giernat, Y., Keppler, O. T., Malim, M. H. & Schaller, T., 8 Jun 2016, In: Journal of Virology. 90, 16, p. 7469-7480 12 p.Research output: Contribution to journal › Article › peer-review
Oligomerization requirements for MX2 mediated suppression of HIV-1 infection
Dicks, M. D. J., Goujon, C., Pollpeter, D., Betancor, G., Apolonia, L., Bergeron, J. & Malim, M. H., Jan 2016, In: Journal of Virology. 90, 1, p. 22-32 11 p.Research output: Contribution to journal › Article › peer-review
Promiscuous RNA Binding Ensures Effective Encapsidation of APOBEC3 Proteins by HIV-1
Apolonia, L., Schulz, R., Curk, T., Rocha, P., Swanson, C. M., Schaller, T., Ule, J. & Malim, M. H., 15 Jan 2015, In: PL o S Pathogens. 11, 1, p. 1-22 22 p., e1004609.Research output: Contribution to journal › Article › peer-review
Immune evasion activities of accessory proteins Vpu, Nef and Vif are conserved in acute and chronic HIV-1 infection
Mlcochova, P., Apolonia, L., Kluge, S. F., Sridharan, A., Kirchhoff, F., Malim, M. H., Sauter, D. & Gupta, R. K., 30 Mar 2015, In: Virology. 482, p. 72-78 7 p.Research output: Contribution to journal › Article › peer-review
Nuclear import of SAMHD1 is mediated by a classical karyopherin alpha/beta 1 dependent pathway and confers sensitivity to Vpx(MAC) induced ubiquitination and proteasomal degradation
Schaller, T., Pollpeter, D., Apolonia, L., Goujon, C. & Malim, M. H., 8 Apr 2014, In: Retrovirology. 11, 16 p., 29.Research output: Contribution to journal › Article › peer-review
PhD Students
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