Furthermore, we show that the extreme N-terminal region is highly conserved for the alpha-PVs. L1 are in fact the most variable regions among the alpha-PVs. We also identify regions of L2, involved in interaction with L1, as evolutionarily conserved among the members of alpha- PVs. Finally, a predicted three-dimensional model was generated to further elucidate probable Angiotensin (1-7) aspects of the L1 and L2 interaction. == Background == Papillomaviruses (PVs) are small, non-enveloped, double-stranded DNA viruses identified as the primary etiological agent in cervical cancer and their potential for malignant transformation in mucosal tissue is a major health concern. Papillomaviruses (PVs) have also been linked to benign cutaneous lesions and with some non-melanoma skin cancers. These viruses are very common pathogens of epithelial surfaces that account for a variety of proliferating lesions in humans and animals. In the past few years, the available number of complete HPV genomic sequences has increased substantially to comprise more than 150 GenBank entries (2007). The PV familyPapillomaviridaeis organized into multiple genera based on sequential parsimony, host range, tissue tropism, and histology. We focused this analysis Angiotensin (1-7) on the late gene products, major (L1) and minor (L2) capsid proteins of the familyPapillomaviridaegenusAlpha-papillomavirus. Alpha-PVs preferentially infect oral and anogenital mucosa of humans and primates with varied risk of oncogenic transformation. Two members of the genusAlpha-papillomavirusare also associated with cutaneous lesions, Human papillomavirus (HPV) 2 and HPV10. The alpha genus includes twelve cutaneous HPV types and two simian PVs [1]. HPVs of the alpha genus are also sub-categorized based on associated risk of oncogenic transformation into Low Risk (LR) and High Risk (HR) genotypes. The HR group includes 19 HPV genotypes (types 16, 18, 26, 31, 33, Angiotensin (1-7) 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68a, 73, 82, 82subtype) and 13 are grouped as LR (types 6, 6a, 6b, 11, 40, 42, 43, 44, 54, 61, 70, 72 and 81) according to epidemiological evidence [2]. Infection with HR HPV genotypes such as HPV 16 and HPV 18 has been directly related to the subsequent development of cervical cancer [3,4]. PV genomes are characterized by eight well-defined open reading frames (ORFs), which are all transcribed from the same DNA strand and orientation. The translated proteins are classified as “early” (E) or “late” (L) based on their temporal expression. The viral ORFs include 3 regulatory genes involved in transcription and replication (E1, E2, and E4), 3 oncogenes (E5, E6, and E7), and 2 genes encoding for self-assembling proteins which constitute the viral COL5A2 capsid (L1 and L2) [5]. PV capsids are approximately 600 A (50 nm) Angiotensin (1-7) in diameter and composed of 72 pentameric capsomeres arranged in a T = 7 icosahedral lattices [6]. The PV capsid proteins L1 and L2 are synthesized late in the infection cycle and function to encapsidate the closed circular double-stranded DNA mini-chromosome [7]. The 72 viral capsomeres are composed of L1 protein pentamers, and the capsomeres are associated with 12 or more copies of the L2 protein. Recombinant L1 or L1 and L2 can be generated in a variety of expression systems to produce self-assembled virus-like particles (VLPs), which approximate the structure of native virions [8,9]. The structure of “small,” T = 1 VLPs assembled from HPV16 L1 expressed inEscherichia colihas recently been resolved at a resolution of 3.5-A [10]. Moreover, the crystal structure of L1 major capsid protein provides insights into the conformation of neutralizing epitopes, potential receptor binding sites, the nature of inter-capsomeric contacts [6] and interactions with L2. High levels of neutralizing antibodies can be generated after immunization with HPV L1 VLPs producing highly type-specific neutralization activity [11,12]. Conformational epitopes and the location of epitopes are critical for the production of neutralizing antibodies [13,14]. It has been suggested that L1 loops extending toward the outer surface of the capsomere contain type specific epitopes [6]. Studies with monoclonal antibodies suggest epitopes composed of FG and HI loops are important for HPV 16 [15] neutralization whereas BC, DE, and HI loops are important for neutralization of HPV 6 and 11 [16]. It has also been.