Identification of a mengovirus protein with anti-interferon activity

Robert Willis King, Purdue University

Abstract

Many cells produce the antiviral protein, interferon, in response to infection by virus. Viruses differ in their response to the antiviral state induced by interferon. The DNA-containing viruses, herpes simplex virus and vaccinia virus, are quite resistant to interferon, whereas RNA-containing viruses, such as vesicular stomatitis virus and the picornaviruses (poliovirus, rhinovirus, foot-and-mouth disease virus, and mengovirus) are very sensitive. Simon, et al. (1976) discovered a mutant of mengovirus, is-1, that when grown under the proper conditions exhibits a 100-1000 fold increase in its sensitivity over the wild type virus, is$\sp+$. The is-1 phenotype can be reversed when interferon-protected mouse cells are coinfected with either vaccinia or is$\sp+$. This thesis demonstrates that is-1 can also be rescued by virus-free cell lysates prepared from mouse L-cells that had been infected with is$\sp+$, as well as with inactivated is$\sp+$ virions. Is-1 could also be rescued by pentameric subunits that were obtained by treating is$\sp+$ at pH6.2. However, when the is$\sp+$ pentameric subunits were further broken down to monomeric subunits by 1.5M urea, is-1 was no longer rescued. Studies on the stability of both is$\sp+$ and is-1 at pH2.0 have shown that is-1 is much more sensitive than is$\sp+$. Revertants that have lost their pH sensitivity also lose their interferon sensitivity. These observations suggest that the is$\sp+$ pentameric subunit not only has a structural function but also has anti-interferon activities. The mutation responsible for the is-1 phenotype has eliminated activity.

Degree

Ph.D.

Advisors

Simon, Purdue University.

Subject Area

Microbiology|Immunology

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