Dr. Neeltje Kootstra has been appointed as Professor of Immune Pathogenesis of Viral Infections and Interventions at Amsterdam UMC. Her chair is embedded within the Department of Experimental Immunology (EXIM), part of Division 9: Laboratories of Amsterdam UMC, and is affiliated with the Infectious Diseases program of the Amsterdam Institute for Immunology and Infectious Diseases (AI&I).
Understanding the immune response to viruses
Prof. Kootstra's research focuses on the immune pathogenesis of viral infections such as HIV, Hepatitis B Virus (HBV), and SARS-CoV-2. Her work explores how the immune system responds to invading viruses, and how viruses, in turn, evolve to escape immune detection.
Prof. Kootstra: ‘From a young age, I have been fascinated by viruses. Despite their size, simplicity and dependence on a host to replicate, they can cause serious diseases. What intrigued me further was how people can respond so differently to infection. Some get severely ill, while others barely get sick at all’.
The HIV/AIDS epidemic of the 1980s, a deadly, misunderstood crisis marked by rapid spread, stigma and slow government response, inspired Prof. Kootstra to pursue a career in HIV research. While HIV is no longer a death sentence thanks to antiretroviral therapy (ART), Prof. Kootstra emphasizes: ‘There is still no cure’.
People living with chronic infections like HIV and HBV often require lifelong antiviral therapy to suppress viral replication. Though effective, this treatment does not eliminate the virus. Moreover, inaccessibility to therapy especially in limited resource countries, may lead to ongoing transmission of the virus.
Toward an HIV cure
Prof. Kootstra’s lab is dedicated to finding a cure for HIV. Although ART effectively inhibits HIV replication, the infection is not cleared and HIV remains present in the immune system. These, infected immune cells (the HIV reservoir) remain hidden from immune detection by not expressing viral proteins. When ART is stopped, these reservoirs reignite infection. This HIV reservoir is a key obstacle in finding a cure for HIV. “One line of research in my lab is characterizing the viral reservoir to develop strategies to eliminate it. Through RNA sequencing, we have identified host pathways that regulate viral latency, and we are now testing compounds and biologicals to target these pathways,” she says.
Another barrier to a HIV cure is residual immune system damage caused by HIV, that remains after the start of ART. This impairs the immune system's ability to recognize and eliminate infected cells. Prof. Kootstra and colleagues have identified several genetic and immunological determinants that are associated with HIV control. They are currently investigating ways to enhance HIV-specific immune responses for long-term control of the virus.
Collaboration
Prof. Kootstra emphasizes that collaboration is essential to scientific progress: ‘Understanding and curing chronic infections requires multidisciplinary teams—epidemiologists, clinicians, virologists, immunologists, and biostatisticians all working together’. She is particularly pleased with the strong collaborations that already exist between the Department of Experimental Immunology (EXIM) and medical microbiology, internal medicine, as well as external partners such as the Public Health Service (GGD) and the HIV Monitoring Foundation.
Text: Esmée Vesseur