Arch Virol (2006) 151: 2321–2335
Modulation of apoptosis by human papillomavirus (HPV)
T. O. Garnett and P. J. Duerksen-Hughes
Department of Biochemistry and Microbiology, Center for Molecular Biology and Gene
Therapy, Loma Linda University School of Medicine, Loma Linda, CA, U.S.A.
Received April 12, 2006; accepted June 12, 2006
Published online July 27, 2006
Summary. The regulation of host-mediated apoptosis by the E6 and E7 onco-
proteins has garnered attention because it is believed to be an important strategy
employed by high-risk (HR)-human papillomaviruses (HPVs) to evade immune
surveillance. Additionally, the revelation that E5 can protect cells from tumor
necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis
suggests that it may also play a role in undermining host defense mechanisms.
Cellular transformation is an unintended consequence of persistent infection by
HR-HPVs, and it is therefore likely that the primary function of E5, E6 and E7 is
to regulate cell survival throughout the normal viral life cycle in order to ensure
viral replication and promote the spread of progeny. The purpose of this article
is to review the literature on the regulation of host-mediated apoptosis by E5, E6
and E7 that describes the mechanisms employed by HR-HPVs to persist in the
host and create the conditions necessary for cellular transformation.
Human papillomaviruses (HPVs) are small, nonenveloped, double-stranded DNA
viruses whose natural cellular hosts are keratinocytes. Infection with HPV occurs
below the surface of the epithelium in the basal layer, and the life cycle of the
virus is closely connected with the differentiation program of the cells it infects.
The most common phenotypical manifestations of HPV infection are warts and
papillomas of the skin, and various genital hyperplastic epithelial lesions. Over 100
HPV genotypes have been identiﬁed and approximately 33% of these genotypes
are associated with lesions of the genital tract. HPVs that infect the genital tract
can be subdivided into two categories: low-risk and high-risk. Low-risk (LR)-
HPVs such as types 6 and 11 generally cause benign warts which rarely progress