Viruses pose a significant threat to human health based on their ability to cause diseases such as acquired immunodeficiency syndrome (AIDS), influenza, hepatitis, cancer, severe acute respiratory syndrome (SARS), hemorrhagic fever and the common cold. Quantitative assessments of virus infectivity are important in the clinic to test the performance of anti-viral drugs on patient isolates as well as to assess the effectiveness of drug treatments over time. Measures of infectivity are also important in basic research to elucidate the molecular-level mechanisms of virus growth and develop effective anti-viral therapeutics or strategies. Established methods for the determination of virus infectivity, such as the plaque assay, lack sensitivity and are both time consuming and labor intensive to implement. The objective of this Technology Development for Biomedical Applications Grant (R21) is to develop a better way to measure the infectivity of viruses. The proposed method: (a) uses micro-scale fluid flows to control and enhance the growth and spread of viruses on host-cell cultures, and (b) employs digital imaging to characterize and quantify spatial patterns of infection. As a model system the flow-enhanced spread of vesicular stomatitis virus (VSV) will be studied because VSV can be readily cultured in the laboratory and is minimally pathogenic to humans. Preliminary results demonstrate for the first time that it is feasible to implement, detect, and enhance the spread of virus infections in a microfluidic channel.
Specific aims of the proposed project will be to: (1) characterize how fluid flow influences virus production by infected cells, (2) elucidate the effects of fluid flow on the morphology of infection comets formed in micro-channels, and (3) employ comet-size distributions to characterize drug resistance in virus populations. The methodology established by this research will set a basis for advancing the characterization of viruses of human medical importance. Viruses cause diseases such as AIDS, influenza, and cancer, and thereby pose a significant risk to public health. Measurements of virus infectivity are important for diagnosing disease in patients and prescribing effective treatments, but current measurement methods lack sensitivity and are labor-intensive to perform. The proposed research aims to address these limitations by advancing a new approach that is both more sensitive and easy to perform.
| Anekal, Samartha G; Zhu, Ying; Graham, Michael D et al. (2009) Dynamics of virus spread in the presence of fluid flow. Integr Biol (Camb) 1:664-71 |
