Human Papillomaviruses

Abstract

Human papillomaviruses (HPV) are a family of small DNA tumor viruses with a size of ~52-55. The family consists of ~200 different genotypes; many of the types cause benign warts or papilloma, while a small fraction of oncogenic or "highrisk" types can cause invasive cervical cancer or other tumors. HPV infects keratinocytes in the basal layer of stratifi ed squamous epithelia and replicates in the nucleus of infected keratinocytes along with keratinocyte differentiation. The viral genome in size of ~7.9 kb encodes six early, non-structural regulatory proteins (E1, E2, E4, E5, E6, and E7) and two late structural proteins (L1 and L2). E6 and E7 are two oncoproteins responsible for the viral oncogenesis of high-risk HPVs, including HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 73, and 82. L1 is a major structural component of viral capsid and its self-assembly in vitro into a viral-like particle (VLP) provides the basis of prophylactic vaccines against infections of several HPV types. In addition to cervical cancer, high-risk HPVs are associated with the development of various anogenital cancers and certain head and neck cancers. A Brief History and Classifi cation of Human PapillomavirusesHuman papillomaviruses (HPV) are a family of small DNA tumor viruses in size of ~52-55 nm in diameter measured initially under electron microscope from skin papillomas by Joseph Melnick at Yale in 1950(Strauss et al. 1950. Since discovery of the fi rst two genotypes of HPV, HPV1 and HPV2, in 1977 (Orth et al. 1977 ) and (Danos et al. 1982 ), the family has grown to consist of ~200 different genotypes, with 185 genotypes being completely sequenced and deposited in GenBank ( www.pave.niaid.nih.gov ). Papillomaviruses were initially classifi ed as a subfamily of the family Papovaviridae in 1962 (Melnick 1962 ), but reclassifi ed in 2002 as an independent family, Papillomaviridae , in the seventh Report of the International Committee on Taxonomy of Viruses (ICTV). The family Papillomaviridae currently contains at least 29 genera and human papillomaviruses are classifi ed into fi ve (alpha, beta, gamma, mu, and nu) genera ( Fig. 7.1 ). The classifi cation of papillomaviruses depends on the most conserved L1 ORF by genotyping. Different genera share less than 60 % nucleotide sequence identity in the L1 ORF. A new type of papillomavirus is given when its DNA sequence of L1 ORF differs by more than 10 % from the closest known HPV type. Otherwise, a subtype indicates the difference between 2 and 10 % and a variant less than 2 %. HPV types are numbered in the order by their discovery. HPVs in the alpha genus cause mucosal and a fraction of cutaneous HPV lesions, while HPVs in the beta, gamma, mu, and nu genera cause cutaneous lesions (de Villiers et al. 2004 ;Bernard et al. 2010 ).HPVs are also grouped clinically as high-risk (oncogenic) types, which are frequently associated with invasive cervical cancer, and low-risk (non-oncogenic) types, which are found mainly in genital warts. Epidemiologic studies of HPV types asso...

Viral DNA Replication Orientation and hnRNPs Regulate Transcription of the Human Papillomavirus 18 Late Promoter

“…HPVs are small DNA viruses. Their genomes are circular and approximately 8 kb in size and encode eight major proteins, six (E1, E2, E4, E5, E6, and E7) located in the “early” region and two (L1 and L2 capsid proteins) in the “late” region ( 4 ). The early proteins regulate viral and host gene expression and play roles in viral DNA maintenance and amplification and pathogenesis.…”

“…The early proteins regulate viral and host gene expression and play roles in viral DNA maintenance and amplification and pathogenesis. L1 and L2 form the virus capsid required for virus morphogenesis, transmission, and survival under the various environmental conditions ( 4 ).…”