Kouacou V. Konan, PhD
Areas of Study
Molecular mechanism of Flavivirus replication and spread
- Indiana University1995PhD
The current focus of my laboratory is to understand the molecular and cellular mechanism of positive-stranded RNA virus replication and spread. Our model system encompasses the Flaviviridae family of viruses such as Zika virus (ZIKV), Dengue virus (DENV) and hepatitis C virus (HCV). ZIKV, DENV and HCV remain a global health threat. For example, the recent ZIKV outbreak has been linked to thousands of cases of severe birth defects and Guillain-Barre syndrome in the Americas. DENVis known to infect 50-100 million people worldwide each year, with mild cases resembling flu-like symptoms and major complications including deadly dengue hemorrhagic fever. HCV is the causative agent of chronic liver disease in among 60 to 100 million people worldwide.With the advent of direct-acting antivirals, great strides have been achieved in combating HCV infection in the developed world. However, there is an emergence of drug-resistant HCV strains. Additionally, there are no direct-acting antivirals targeting ZIKV or DENV infection. Finally, there is no effective vaccine against any of these viruses.
Role of nonstructural proteins in virus replication.
ZIKV, DENV and HCV replicate and assemble their genomes in the cytoplasm of infected cells. Notably, these viruses are known to generate novel membrane platforms to replicate their genomes. In addition, they hijack host membrane lipids to package their genomes and produce new virus particles. A major interest in our laboratory is to understand how nonstructural proteins (NS1-NS2A-NS2B-NS3-NS4A-NS4B-NS5 for ZIKV and DENV; NS2-NS3-NS4A-NS4B-NS5A-NS5B for HCV) modulate viral genome replication, particle production and virus spread in vitro and in vivo. We are currently working with Laura Kramer (Wadsworth Center) and Michael Robek (Albany Medical College) to determine how changes in ZIKV nonstructural proteins modulate protein function, virus infectivity in insect, mammalian cells or IFNAR-deficient mice. These studies are conducted in DENV as well.
Role of host factors in virus replication.
ZIKV, DENV and HCV need to antagonize restriction factors and exploit proviral factors to successfully replicate in the host. One goal of my lab is to utilize biochemical and genetic means to identify novel host dependency factors as well as restriction factors. This study is done in collaboration with Laura Kramer (Wadsworth Center), Michael Robek (Albany Medical College) and Harvard University School of Medicine. We have already identified host dependency factors for HCV replication. Ongoing study focuses on identifying host factors crucial for modulating ZIKV infectivity in vitro and in vivo.
Role of host lipid metabolism in virus replication.
ZIKV, DENV and HCV are enveloped positive-stranded RNA viruses. They rely on host membranes for entry, genome replication and virus maturation. However, the role of various lipids in the replication of these viruses is not well understood. We have evidence that glycosphingolipids are key players in HCV genome replication. Ongoing study focuses on the role of lipid modification, and novel lipid metabolic proteins, in ZIKV replication in vitro and in vivo. This study is also done in collaboration with Laura Kramer (Wadsworth Center) and Michael Robek (Albany Medical College).
Khan I, Katikaneni DS, Han Q, Sanchez-Felipe L, Hanada K, Ambrose RL, Mackenzie JM, and Konan KV. 2014. Modulation of Hepatitis C Virus Genome Replication by Glycosphingolipids and Four-Phosphate Adaptor Protein 2. J. Virol.88, 12276-12295.
Konan KV and Sanchez-Felipe L. 2014. Lipids and RNA virus replication. Current Opinion in Virology 9, 45-52.
Fan B, Lu KY, Sutandy FX, Chen YW, Konan KV, Zhu H, Kao CC, and Chen CS. 2013. A human proteome microarray identifies that the heterogeneous nuclear ribonucleoprotein K (hnRNP K) recognizes the 5 ' terminal sequence of the hepatitis C virus RNA. Mol. Cell. Proteomics13.1, 84-92.
View Kouacou V. Konan's articles on the National Institute of Health's PubMed website.