Research in the Akhtar Laboratory is focused on understanding how viruses infect and cause pathogenesis in the pediatric brain. The approach that the researchers take is to identify clinical viral isolates associated with pediatric infection and poor neurologic outcomes, and bring these isolates back to the lab to assess the mechanism by which this occurs. They use viral whole genome sequencing, human and murine neuronal in vitro models, and murine in vivo models, as well as reverse genetics to understand clinical viral virulence factors. The current focus of the lab is to determine virulence factors contributing to neonatal herpes simplex virus encephalitis.
Herpes Simplex Virus
Lisa Akhtar, MD, PhD
NEUROVIRULENCE DETERMINANTS OF NEONATAL HERPES SIMPLEX VIRUS (HSV) DISEASE
The purpose of this research is to understand the role of viral genetic variability in determining the clinical manifestations of neonatal HSV disease, particularly the ability to infect the neonatal brain. Herpes simplex virus (HSV) infection of the neonatal brain causes severe encephalitis and permanent neurologic deficits, but the factors that promote central nervous system (CNS) infection are not known. Recent studies show that substantial genetic variability exists within HSV genomes, but have not evaluated how these variations impact viral growth characteristics or human disease manifestations. Dr. Akhtar and her research team are working to identify HSV genetic variations associated with neonatal CNS disease, determine their impact on viral spread between neurons, and their ability to alter progression to CNS infection. Their approach includes large-scale viral genomic sequencing to identify variations most frequently associated with CNS disease, followed by creation of mutant viruses to determine the individual impact of identified variations on viral neuron-to-neuron spread as well as progression to encephalitis in murine models. These studies will provide the first insights into how variations in the neonatal HSV genome impact neurovirulence and the development of CNS disease.
DETERMINATION OF HERPES SIMPLEX VIRUS (HSV)-1 SEROPREVALENCE IN EARLY CHILDHOOD
The purpose of this research is to determine the seroprevalence of HSV-1 in early childhood. Although the vast majority of older adults in the United States have been infected with HSV-1 during their lifetime, we do not understand exactly when most children are exposed. This information is important to determine the optimal age of vaccination when a preventative vaccine is ultimately available. Therefore, Dr. Akhtar and her research team are currently evaluating a cohort of children age 6 months to 18 years for exposure to the virus, to better understand when seroconversion occurs.