Proteolytic Regulation of HPV Infection

NIH Pandemic-Era Grants

Pandemic Era Grants

2021

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Principal Investigator: Gonzalo  Izaguirre
Organization: UNIVERSITY OF ILLINOIS AT CHICAGO
Fiscal Year: 2021
Award: $197,894
Funding agency: National Institute of Allergy and Infectious Diseases

Abstract
Many human pathogenic viruses exploit the host-cell proteases of the proprotein
convertase (PC) family for their own benefit. The proteolytic processing of viral surface
proteins is a mechanism by which viruses regulate their infectivity. The crucial role of
the proteolytic regulation of viral maturation and replication makes PCs a feasible target
for antiviral intervention. We have found that the highly oncogenic HPV types, HPV16
and HPV18, differ in their PC selectivity along the same line that divides the two PC
reaction specificity groups composed of furin and PC5/PACE4/PC7. It is hypothesized
that the interplay of HPV-type PC reactivity and the PC gene expression profile of
keratinocytes at anatomical sites of HPV infection may determine known HPV-type
differences in cell tropism and infectivity. Our long term goals are to gain insight into
the details of this widespread mechanism of virus replication control system and
strengthen the notion that PC inhibition is a viable antiviral strategy. In order to
test this hypothesis, it will be investigated first, the differences in PC reactivity and
selectivity of high-risk and low-risk HPV types, including the characterization of three
potential PC cleavage sites. And second, the dependence of HPV-type infectivity on
the PC genes expression of keratinocytes at various anatomical sites of HPV infection.

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