HPV18 E1^E4 is assembled into aggresome-like compartment and involved in sequestration of viral oncoproteins.

Abstract

Papillomavirus is the etiological agent for warts and several squamous carcinomas. Skin cancer induced by cottontail rabbit papillomavirus was the first animal model for virus-induced carcinogenesis. The target organ of the virus infection is stratified epithelium and virus replication is tightly regulated by the differentiation program of the host cell. E1^E4 protein is a viral gene product, and although it is considered to be involved in the control of virus replication, little is known about the biological role. We found that HPV18 E1^E4 was assembled into an aggresome-like compartment and was involved in sequestration of virus oncoproteins, which might contribute to the differentiation-dependent lifecycle of papillomavirus.

The viral replication organelles within cells studied by electron microscopy

“…Due to their complex composition and functions, virus factories could be contemplated as the living state of viruses . Two main pathways have been identified so far as being responsible for viral factory biogenesis: aggresome formation for DNA viruses and autophagy for RNA viruses (Abernathy et al, 2019;Jackson et al, 2005;Kajitani et al, 2013;Wileman, 2007). Fig.…”

Virus-Induced Cytoplasmic Aggregates and Inclusions Are Critical Cellular Regulatory and Antiviral Factors

“…The sequestration of viral proteins into inactive aggregates reduces their activity. Findings by Kajitani et al (2013), showed that human papillomavirus 18 (HPV 18)-infected cells formed aggresome-like compartments at the perinuclear site of the host cells. The major viral oncoproteins E6 and E7 were recruited and sequestrated as an insoluble fraction in these aggresome-like compartments.…”

“…The major viral oncoproteins E6 and E7 were recruited and sequestrated as an insoluble fraction in these aggresome-like compartments. These compartments, like classical aggresomes, associate with the vimentin cage and are assembled by dynein-dependent retrograde transport along microtubules filaments [55]. The sequestration of viral proteins renders them susceptible to autophagy and results in suppressed viral pathogenesis.…”

Animal model studies on viral infections

“…Ohsugi et al ( 2013 ) have reported that natural infection status of laboratory mice by murine norovirus. Finally, Kajitani et al ( 2013 ) have described the possible involvement of E1 ∧ E4 protein of human papillomavirus type 18 in its differentiation-dependent life cycle.…”