Research Description

Parvovirus B19-Brain-thyroid interactions: effect of B19 NS1 on Thyroid Hormone Receptor Gene Expression

Parvovirus B19 (B19), a human pathogen, is one of the smallest DNA-containing viruses that infect humans. The genome is a single-stranded DNA that encodes for a nonstructural protein, NS1, and two capsid proteins, VP1 and VP2. B19 has been known to cause autoimmune responses and is linked with many syndromes, including Hashimoto’s thyroiditis. B19 has also been shown to infect and possibly persist in the brain, and we are interested in whether B19 may play a role in the pathogenesis of neuropsychiatric disorders, such as bipolar disorder, which has been associated with virus infections, autoimmunity, and thyroid problems. The related murine parvovirus minute virus of mice (MVM) NS1 has been found to upregulate thyroid hormone receptor (THR) gene expression in contrast to its usual downregulatory effect on gene expression. We want to establish whether the B19 NS1 also has a similar effect on THR gene expression. In this project we will determine if B19 infection modulates THR gene expression in the brain. First, the levels of mRNA for THR in 3 different cell lines will be tested by reverse transcriptase polymerase chain reaction (RT-PCR). Then the mRNA levels will be determined in the same cell lines that have been either transfected with plasmid constructs that encode for the B19 NS1 protein or infected with AAV-B19 hybrid virus to mimic wild-type B19 infection. Based on how MVM NS1 increases THR gene expression, we expect THR gene expression to increase with B19 NS1 expression under conditions of transfection or infection. These studies will lead to a better understanding of how B19 may play a role in brain and thyroid pathogenesis.