Pleiotropic mechanisms of virus survival and persistence

Abstract

Viruses are enormously efficient infectious agents that have been implicated in causing human disease for centuries. Transmission of these pathogens continues to be from one life form to another in the form of isolated cases, epidemics, and pandemics. Each infection requires entry into a susceptible host, replication, and evasion of the immune system. Viruses are successful pathogens because they target specific cells for their attack, exploit the cellular machinery, and are efficient in circumventing and/or inhibiting key cellular events required of survival. This article reviews some of the advances that have taken place in human virology in the past 50 years, emphasizing mechanisms that contribute to, and are involved with, virus survival and persistence.

Epithelial maturation and molecular biology of oral HPV

“…It is also associated with down-regulation of gap junction intercellular communications, with expression of major histocompatibility complex (MHC) class 1 molecules, and with activation of growth factor receptors. Thus E5 protein has the capacity to promote immune evasion [34,36]. …”

“…During productive HPV infection high- and low-risk HPV E6 and E7 facilitate the maintenance of the viral episome in suprabasal matured epithelial cells [3]. E6 and E7 also play an important rôle in the increased cell proliferation and the extended cell survival of HPV-associated malignancies, by altering the cell cycle regulatory factors [36,37]. E6 of high-risk HPV can induce ubiquitin-mediated degradation of p53 tumour suppressor protein [38,39]; and E7 of high-risk HPV genotypes can bind to and inactivate the Rb suppressor gene and other cellular proteins associated with cell cycle regulation [39,40].…”

Human papillomavirus-mediated carcinogenesis and HPV-associated oral and oropharyngeal squamous cell carcinoma. Part 1: Human papillomavirus-mediated carcinogenesis

“…High-risk HPV E6 and E7 oncoproteins expressed in epithelial cells infected with HPV are implicated in the increased proliferation and in the abnormal differentiation of these cells [16,17]. When the E6/E7 proteins are the expression of infection of the cell with low-risk HPV, then these active proteins may induce benign neoplasms.…”

“…E6 and E7 oncoproteins can inactivate the genetic mechanisms that control both the cell cycle and apoptosis [16,17]. The hallmark of high-risk HPV E6 oncogenic activity is degradation of the p53 tumour-suppressor gene.…”

“…The hallmark of high-risk HPV E6 oncogenic activity is degradation of the p53 tumour-suppressor gene. The functions of p53 in the cell cycle include controlling the G1 transition to the S phase of the cell cycle at the G1 checkpoint by inducing expression of cyclin inhibitors p16, p21 and p27 that block the activities of cyclin-CDKs (cyclin-dependant kinase) complexes, thus mediating arrest of the cell cycle by blocking the progression of the cell cycle at the G1/S transition [17]. …”