Dr Najla Nasr

Senior Research Fellow
The Westmead Institute for Medical Research, Westmead Clinical School

Telephone 02 8627 3622

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In the media

New knowledge on how HIV beats the body’s early immune response

September 14, 2017Print

In an important step towards eradicating HIV-associated viral reservoirs, researchers have identified how the HIV virus hijacks the innate immune system to facilitate its replication and spread, thus gaining a foothold infection in the body.

The findings, published in the Journal of Virology, show how HIV induces antiviral interferon stimulated genes in the absence of interferon production.

Lead author of the study, Dr Najla Nasr said it’s like a prize fight, with both HIV and the body’s immune response both fighting for supremacy.

“When a person is infected with HIV, the virus infects immune cells and knocks out the body’s interferon production; the first line of defence in our bodies.

“When interferon production is inhibited, the virus infects adjacent cells and spreads throughout the body.

“Surprisingly, we found that although HIV inhibits interferon production it also stimulates more than twenty antiviral interferon-stimulated genes—or ISGs—in its key target cells. This is the largest effect yet shown by any individual virus.

“ISGs are critical for controlling virus infections. They provide the earliest protective response to counter invading pathogens, but paradoxically they can also contribute to virus persistence.

“For its own survival advantage, HIV induces these genes in order to survive and spread throughout the body,” Dr Nasr explained.

Dr Nasr said the ultimate goal of this research was to understand how these antiviral genes are induced and thus coming up with strategies to boost their expression so that the virus replication is not just slowed but completely stopped.

The Journal of Virology is ranked as the top journal exploring the nature of viruses.

The full research paper is available under PMID: 28768867

Selected grants

2016

  • Restoring interferon production by myeloid cells infected with HIV by gene therapy; Cunningham A, Harman A, Diefenbach R, Nasr N, Kizana E; Australian Centre for HIV and Hepatitis Virology Research (ACH2)/Research Support.
  • Defining the Interaction of HIV with the Interferon System in Initial Mucosal Infection; Cunningham A, Harman A, Palmer S, Nasr N, Diefenbach R, Sandgren K; National Health and Medical Research Council (NHMRC)/Project Grants.

2015

  • The Role of Dendritic Cells in Sexual Transmission of HIV and Viral Reservoir Formation; Harman A, Cunningham A, Palmer S, Kim M, Nasr N; National Health and Medical Research Council (NHMRC)/Project Grants.

2014

  • Development of small molecule inhibitors of HIV envelope-Langerin interactions and of HIV uptake by Langerhans Cells (LCs) as topical (genital) microbicides; Cunningham A, Nasr N, Diefenbach R; Australian Centre for HIV and Hepatitis Virology Research/Research Grant.

Selected publications

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Book Chapters

  • Nasr, N., Harman, A., Turville, S., Cunningham, A. (2014). HIV infection of dendritic cells. In Elisa Vincenzi, Guido Poli (Eds.), Human Retroviruses: Method and Protocols, (pp. 221-232). New York: Humana Press. [More Information]
  • Cunningham, A., Harman, A., Kim, M., Nasr, N., Lai, J. (2013). Immunobiology of Dendritic Cells and the Influence of HIV Infection. In Li Wu, Olivier Schwartz (Eds.), HIV Interactions with Dendritic Cells: Infection and Immunity, (pp. 1-44). New York, USA: Springer Science+Business Media. [More Information]

Journals

  • Botting, R., Rana, H., Bertram, K., Rhodes, J., Baharlou, H., Nasr, N., Cunningham, A., Harman, A. (2017). Langerhans cells and sexual transmission of HIV and HSV. Reviews in Medical Virology, 27(2), e1923. [More Information]
  • Nasr, N., Alshehri, A., Wright, T., Shahid, M., Heiner, B., Harman, A., Botting, R., Helbig, K., Beard, M., Suzuki, K., Cunningham, A., et al (2017). Mechanism of interferon-stimulated gene induction in HIV-1- infected macrophages. Journal of Virology, 91(20). [More Information]
  • Ng, W., Londrigan, S., Nasr, N., Cunningham, A., Turville, S., Brooks, A., Reading, P. (2016). The C-type lectin langerin functions as a receptor for attachment and infectious entry of influenza A virus. Journal of Virology, 90(1), 206-221. [More Information]
  • Marsden, V., Donaghy, H., Bertram, K., Harman, A., Nasr, N., Keoshkerian, E., Merten, S., Lloyd, A., Cunningham, A. (2015). Herpes Simplex Virus Type 2–Infected Dendritic Cells Produce TNF-a, Which Enhances CCR5 Expression and Stimulates HIV Production from Adjacent Infected Cells. The Journal of Immunology, 194(9), 4438-4445. [More Information]
  • Harman, A., Nasr, N., Feetham, A., Galoyan, A., Alshehri,, A., Rambukwelle, D., Botting, R., Hiener, B., Diefenbach, E., Diefenbach, R., Kim, M., Cunningham, A., et al (2015). HIV blocks interferon induction in human dendritic cells and macrophages by dysregulation of TBK1. Journal of Virology, 89(13), 6575-6584. [More Information]
  • Kim, M., Truong, N., James, V., Bosnjak, L., Sandgren, K., Harman, A., Nasr, N., Bertram, K., Olbourne, N., Sawleshwarkar, S., Cunningham, A., et al (2015). Relay of herpes simplex virus between Langerhans cells and dermal dendritic cells in human skin. PLoS Pathogens, 11(4), 1-19. [More Information]
  • Nasr, N., Lai, J., Botting, R., Mercier, S., Harman, A., Kim, M., Turville, S., Center, R., Domagala, T., Gorry, P., Cunningham, A., et al (2014). Inhibition of Two Temporal Phases of HIV-1 Transfer from Primary Langerhans Cells to T Cells: The Role of Langerin. The Journal of Immunology, 193(5), 2554-2564. [More Information]
  • Harman, A., Bye, C., Nasr, N., Sandgren, K., Kim, M., Mercier, S., Botting, R., Lewin, S., Cunningham, A., Cameron, P. (2013). Identification of Lineage Relationships and Novel Markers of Blood and Skin Human Dendritic Cells. The Journal of Immunology, 190(1), 66-79. [More Information]
  • Cunningham, A., Harman, A., Nasr, N. (2013). Initial HIV mucosal infection and dendritic cells. EMBO Molecular Medicine, 5(5), 658-660. [More Information]
  • Mercier, S., Donaghy, H., Botting, R., Turville, S., Harman, A., Nasr, N., Ji, H., Kusebauch, U., Mendoza, L., Shteynberg, D., Cunningham, A., et al (2013). The Microvesicle Component of HIV-1 Inocula Modulates Dendritic Cell Infection and Maturation and Enhances Adhesion to and Activation of T Lymphocytes. PLoS Pathogens, 9(10), 1-18. [More Information]
  • Harman, A., Kim, M., Nasr, N., Sandgren, K., Cameron, P. (2013). Tissue dendritic cells as portals for HIV entry. Reviews in Medical Virology, 23(5), 319-333. [More Information]
  • Nasr, N., Maddocks, S., Turville, S., Harman, A., Woolger, N., Helbig, K., Wilkinson, J., Bye, C., Wright, T., Rambukwelle, D., Donaghy, H., Cunningham, A., et al (2012). HIV-1 infection of human macrophages directly induces viperin which inhibits viral production. Blood, 120(4), 778-788. [More Information]
  • Harman, A., Lai, J., Turville, S., Samarajiwa, S., Gray, L., Marsden, V., Mercier, S., Jones, K., Nasr, N., Rustagi, A., Cunningham, A., et al (2011). HIV infection of dendritic cells subverts the interferon induction pathway via IRF1 and inhibits type 1 interferon production. Blood, 118(2), 298-308. [More Information]
  • Huch, J., Cunningham, A., Arvin, A., Nasr, N., Santegoets, S., Slobedman, E., Slobedman, B., Abendroth, A. (2010). Impact of varicella-zoster virus on dendritic cell subsets in human skin during natural infection. Journal of Virology, 84(8), 4060-4072. [More Information]
  • Cunningham, A., Abendroth, A., Jones, C., Nasr, N., Turville, S. (2010). Viruses and Langerhans cells. Immunology and Cell Biology, 88(4), 416-423. [More Information]
  • Harman, A., Kraus, M., Bye, C., Byth Wilson, K., Turville, S., Tang, O., Mercier, S., Nasr, N., Stern, J., Slobedman, B., Cunningham, A., et al (2009). HIV-1-infected dendritic cells show 2 phases of gene expression changes, with lysosomal enzyme activity decreased during the second phase. Blood, 114(1), 85-94. [More Information]
  • Gray, L., Sterjovski, J., Churchill, M., Ellery, P., Nasr, N., Lewin, S., Crowe, S., Wesselingh, S., Cunningham, A., Gorry, P. (2005). Uncoupling coreceptor usage of human immunodeficiency virus type 1 (HIV-1) from macrophage tropism reveals biological properties of CCR5-restricted HIV-1 isolates from patients with acquired immunodeficiency syndrome. Virology, 337(2), 384-398. [More Information]
  • Ewart, G., Nasr, N., Naif, H., Cox, G., Cunningham, A., Gage, P. (2004). Potential New Anti-Human Immunodeficiency Virus Type 1 Compounds Depress Virus Replication In Cultured Human Macrophages. Antimicrobial Agents and Chemotherapy, 48(6), 2325-2330. [More Information]
  • Naif, H., Cunningham, A., Alali, M., Nasr, N., Buhler, M., Stewart, G., Li, S., Schols, D., de Clercq, E. (2002). A Human Immunodeficiency Virus Type 1 Isolate from an Infected Person Homozygous for CCR5/\32 Exhibits Dual Tropism by Infecting Macrophages and MT2 Cells via CXCR4. Journal of Virology, 76(7), 3114-3124. [More Information]
  • Qi, J., Stevens, R., Wadley, R., Collins, A., Cooley, M., Naif, H., Nasr, N., Cunningham, A., Katsoulotos, G., Wanigasekara-Mohotti, Y., Roufogalis, B., et al (2002). IL-16 Regulation of Human Mast Cells/Basophils and Their Susceptability to HIV-1. The Journal of Immunology, 168(8), 4127-4134.

2017

  • Botting, R., Rana, H., Bertram, K., Rhodes, J., Baharlou, H., Nasr, N., Cunningham, A., Harman, A. (2017). Langerhans cells and sexual transmission of HIV and HSV. Reviews in Medical Virology, 27(2), e1923. [More Information]
  • Nasr, N., Alshehri, A., Wright, T., Shahid, M., Heiner, B., Harman, A., Botting, R., Helbig, K., Beard, M., Suzuki, K., Cunningham, A., et al (2017). Mechanism of interferon-stimulated gene induction in HIV-1- infected macrophages. Journal of Virology, 91(20). [More Information]

2016

  • Ng, W., Londrigan, S., Nasr, N., Cunningham, A., Turville, S., Brooks, A., Reading, P. (2016). The C-type lectin langerin functions as a receptor for attachment and infectious entry of influenza A virus. Journal of Virology, 90(1), 206-221. [More Information]

2015

  • Marsden, V., Donaghy, H., Bertram, K., Harman, A., Nasr, N., Keoshkerian, E., Merten, S., Lloyd, A., Cunningham, A. (2015). Herpes Simplex Virus Type 2–Infected Dendritic Cells Produce TNF-a, Which Enhances CCR5 Expression and Stimulates HIV Production from Adjacent Infected Cells. The Journal of Immunology, 194(9), 4438-4445. [More Information]
  • Harman, A., Nasr, N., Feetham, A., Galoyan, A., Alshehri,, A., Rambukwelle, D., Botting, R., Hiener, B., Diefenbach, E., Diefenbach, R., Kim, M., Cunningham, A., et al (2015). HIV blocks interferon induction in human dendritic cells and macrophages by dysregulation of TBK1. Journal of Virology, 89(13), 6575-6584. [More Information]
  • Kim, M., Truong, N., James, V., Bosnjak, L., Sandgren, K., Harman, A., Nasr, N., Bertram, K., Olbourne, N., Sawleshwarkar, S., Cunningham, A., et al (2015). Relay of herpes simplex virus between Langerhans cells and dermal dendritic cells in human skin. PLoS Pathogens, 11(4), 1-19. [More Information]

2014

  • Nasr, N., Harman, A., Turville, S., Cunningham, A. (2014). HIV infection of dendritic cells. In Elisa Vincenzi, Guido Poli (Eds.), Human Retroviruses: Method and Protocols, (pp. 221-232). New York: Humana Press. [More Information]
  • Nasr, N., Lai, J., Botting, R., Mercier, S., Harman, A., Kim, M., Turville, S., Center, R., Domagala, T., Gorry, P., Cunningham, A., et al (2014). Inhibition of Two Temporal Phases of HIV-1 Transfer from Primary Langerhans Cells to T Cells: The Role of Langerin. The Journal of Immunology, 193(5), 2554-2564. [More Information]

2013

  • Harman, A., Bye, C., Nasr, N., Sandgren, K., Kim, M., Mercier, S., Botting, R., Lewin, S., Cunningham, A., Cameron, P. (2013). Identification of Lineage Relationships and Novel Markers of Blood and Skin Human Dendritic Cells. The Journal of Immunology, 190(1), 66-79. [More Information]
  • Cunningham, A., Harman, A., Kim, M., Nasr, N., Lai, J. (2013). Immunobiology of Dendritic Cells and the Influence of HIV Infection. In Li Wu, Olivier Schwartz (Eds.), HIV Interactions with Dendritic Cells: Infection and Immunity, (pp. 1-44). New York, USA: Springer Science+Business Media. [More Information]
  • Cunningham, A., Harman, A., Nasr, N. (2013). Initial HIV mucosal infection and dendritic cells. EMBO Molecular Medicine, 5(5), 658-660. [More Information]
  • Mercier, S., Donaghy, H., Botting, R., Turville, S., Harman, A., Nasr, N., Ji, H., Kusebauch, U., Mendoza, L., Shteynberg, D., Cunningham, A., et al (2013). The Microvesicle Component of HIV-1 Inocula Modulates Dendritic Cell Infection and Maturation and Enhances Adhesion to and Activation of T Lymphocytes. PLoS Pathogens, 9(10), 1-18. [More Information]
  • Harman, A., Kim, M., Nasr, N., Sandgren, K., Cameron, P. (2013). Tissue dendritic cells as portals for HIV entry. Reviews in Medical Virology, 23(5), 319-333. [More Information]

2012

  • Nasr, N., Maddocks, S., Turville, S., Harman, A., Woolger, N., Helbig, K., Wilkinson, J., Bye, C., Wright, T., Rambukwelle, D., Donaghy, H., Cunningham, A., et al (2012). HIV-1 infection of human macrophages directly induces viperin which inhibits viral production. Blood, 120(4), 778-788. [More Information]

2011

  • Harman, A., Lai, J., Turville, S., Samarajiwa, S., Gray, L., Marsden, V., Mercier, S., Jones, K., Nasr, N., Rustagi, A., Cunningham, A., et al (2011). HIV infection of dendritic cells subverts the interferon induction pathway via IRF1 and inhibits type 1 interferon production. Blood, 118(2), 298-308. [More Information]

2010

  • Huch, J., Cunningham, A., Arvin, A., Nasr, N., Santegoets, S., Slobedman, E., Slobedman, B., Abendroth, A. (2010). Impact of varicella-zoster virus on dendritic cell subsets in human skin during natural infection. Journal of Virology, 84(8), 4060-4072. [More Information]
  • Cunningham, A., Abendroth, A., Jones, C., Nasr, N., Turville, S. (2010). Viruses and Langerhans cells. Immunology and Cell Biology, 88(4), 416-423. [More Information]

2009

  • Harman, A., Kraus, M., Bye, C., Byth Wilson, K., Turville, S., Tang, O., Mercier, S., Nasr, N., Stern, J., Slobedman, B., Cunningham, A., et al (2009). HIV-1-infected dendritic cells show 2 phases of gene expression changes, with lysosomal enzyme activity decreased during the second phase. Blood, 114(1), 85-94. [More Information]

2005

  • Gray, L., Sterjovski, J., Churchill, M., Ellery, P., Nasr, N., Lewin, S., Crowe, S., Wesselingh, S., Cunningham, A., Gorry, P. (2005). Uncoupling coreceptor usage of human immunodeficiency virus type 1 (HIV-1) from macrophage tropism reveals biological properties of CCR5-restricted HIV-1 isolates from patients with acquired immunodeficiency syndrome. Virology, 337(2), 384-398. [More Information]

2004

  • Ewart, G., Nasr, N., Naif, H., Cox, G., Cunningham, A., Gage, P. (2004). Potential New Anti-Human Immunodeficiency Virus Type 1 Compounds Depress Virus Replication In Cultured Human Macrophages. Antimicrobial Agents and Chemotherapy, 48(6), 2325-2330. [More Information]

2002

  • Naif, H., Cunningham, A., Alali, M., Nasr, N., Buhler, M., Stewart, G., Li, S., Schols, D., de Clercq, E. (2002). A Human Immunodeficiency Virus Type 1 Isolate from an Infected Person Homozygous for CCR5/\32 Exhibits Dual Tropism by Infecting Macrophages and MT2 Cells via CXCR4. Journal of Virology, 76(7), 3114-3124. [More Information]
  • Qi, J., Stevens, R., Wadley, R., Collins, A., Cooley, M., Naif, H., Nasr, N., Cunningham, A., Katsoulotos, G., Wanigasekara-Mohotti, Y., Roufogalis, B., et al (2002). IL-16 Regulation of Human Mast Cells/Basophils and Their Susceptability to HIV-1. The Journal of Immunology, 168(8), 4127-4134.

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