AbstractsBiology & Animal Science

The outcomes of virus-host interactions determine the pathogenic properties of viruses. Primate lentiviruses and hepacivirus are examples of pathogenic RNA viruses that maintain the abilities to propagate and cause chronic viral diseases in spite of host attempts to impede viral replication. In an attempt to reveal the winning strategies employed by these viruses to evade host antiviral defenses, I have investigated the host responses to the infections of these RNA viruses by functional genomics facilitated by bioinformatics. For primate lentiviruses, I evaluated the infections of human immunodeficiency virus-1 (HIV-1) and simian immunodeficiency virus (SIV) in macaque peripheral blood mononuclear cells, as they had demonstrated distinct pathogenic phenotypes in macaque animals. I found that the expression patterns of immune response genes induced by HIV-1 and SIV infections correlated with their pathogenic properties in vivo, as HIV-1 may up-regulate the expression of immune response genes while SIV may repress their expressions. For hepacivirus, I focused on analyzing the expression patterns of cellular microRNAs and their corresponding target genes in response to the presence of HCV RNA in HCV replicon cells and HCV infected human liver tissues. My data showed that HCV may regulate the expression of both cellular microRNAs and cellular genes in a human liver cell line. More importantly, bioinformatic analyses suggested the relationship between the HCV-associated microRNA and mRNA expressions. A broader implication from this study is that HCV may lift the blockade imposed by the host on its replication utilizing this mechanism. In summary, by monitoring host responses during virus infections from different aspects, I have had a better understanding of the molecular changes inside the cells during virus-host interactions. In particular, my functional genomic studies illustrated changes associated with the infections of primate lentivirus and hepacivirus in the host at the fundamental level of gene expression, which directly impacts the arsenal of genes the host draws upon in mounting an effective anti-viral response, or lack thereof. These exploratory research projects combined with classical molecular biology approaches have contributed valuable information which will hopefully lead to the future development of both novel antiviral therapies and better vaccines.