Developing vaccines against minor capsid antigen L2 to prevent papillomavirus infection

Karanam, Balasubramanyam; Jagu, Subhashini; Huh, Warner K.; Roden, Richard B.S.

doi:10.1038/icb.2009.13

Cited by 63 publications

(61 citation statements)

References 128 publications

(419 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, sequences at the C terminus of L2 have been demonstrated as membrane destabilizing and required for infection (21). Furthermore, transmembrane domain prediction software suggests that a highly conserved transmembrane domain might reside between residues 45 to 67 of HPV16 L2 (22), with equivalent regions in L2 sequences of all other types examined, but none in L1 or VP2 of the polyomaviruses MCV and BKV. Nevertheless, to date, we have failed to detect a consistent cleavage of L2 or L1 upon infection of HaCaT cells with HPV16 pseudovirions that could be blocked by ␥-secretase (or furin) inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Papillomavirus Infection Requires γ Secretase

Karanam¹,

Peng²,

Li³

et al. 2010

J Virol

Self Cite

View full text Add to dashboard Cite

The mechanism by which papillomaviruses breach cellular membranes to deliver their genomic cargo to the nucleus is poorly understood. Here, we show that infection by a broad range of papillomavirus types requires the intramembrane protease ␥ secretase. The ␥-secretase inhibitor (S, The necessary causal association of persistent infection by an "oncogenic" type of human papillomavirus (HPV) with cervical cancer is firmly established (52,53). HPV is the most prevalent sexually transmitted infection, and although the majority of patients clear their infection, HPV is directly responsible for 5% of all cancer deaths worldwide (30). HPV is also associated with multiple other anogenital cancers and oropharyngeal cancers.SThe life cycle of HPV is closely linked to epithelial differentiation within stratified squamous epithelia (16). Initial infection occurs within the undifferentiated proliferative basal cell layer in which only the viral early proteins are expressed, whereas production of the late proteins and, thus, progeny virus is restricted to the terminally differentiated suprabasal compartment (53). The exquisite dependence of virion production upon epithelial differentiation and lack of a rapid phenotype in culture can be circumvented by ectopic expression of the capsid proteins L1 and L2 in cells maintaining viral genome or reporter constructs as episomes, resulting in "quasivirions" or "pseudovirions," respectively, whose infectivity can be readily and rapidly quantified in vitro or in vivo (6,11,35,41).The completion of the entire papillomavirus life cycle is species specific. However, studies with bovine papillomavirus (BPV) in horses and hamsters, HPV pseudovirions in mouse challenge models, and quasivirions in rabbits suggest that virion internalization and delivery of the encapsidated DNA to the nucleus are promiscuous and that tropism is determined at a later stage of the life cycle (11,27,29,39).Although significant progress has been made in understanding the HPV life cycle and virion structure, many of the molecular events of virus internalization and infection are poorly defined (43). Both the L1 (major) and L2 (minor) capsid proteins provide essential functions during infection (41) (8). L1 is sufficient to form empty capsids, termed virus-like particles (VLPs) (25), which bind to basement membrane and to the cell surface and which also form the basis of the licensed HPV vaccines (10). Glycosaminoglycans (GAGs), most notably heparan sulfate (HS), play a critical role in virion binding and infection, both in vitro and in the murine vaginal challenge model, although differences between HPV types and target cells in vitro have been described (14,19,20), for example, between HPV16 and HPV31 (4,34,42). Once bound to the basement membrane, the virions undergo a conformation change resulting in the surface display of the amino terminus of L2 and its cleavage by a proprotein convertase (PC), furin and/or PC5/PC6, and the transfer of virions to the cell surface (24). The uptake of the virions is apparently ...

show abstract

Section: Discussionmentioning

confidence: 99%

Papillomavirus Infection Requires γ Secretase

Karanam¹,

Peng²,

Li³

et al. 2010

J Virol

Self Cite

View full text Add to dashboard Cite

show abstract

“…In confirmation of this, animals immunized with the HPV L2 protein produced neutralizing antibodies for a broad HPV spectrum [50,51]. This observation contrasts sharply with the type-specific protection induced by L1 and suggests the possibility of a simple pan-HPV prophylactic vaccine, based on the L2 protein [49,52,53].…”

Section: A Pan-hpv Vaccinementioning

confidence: 83%

“…For example, HPV-31 and -33 are more commonly found than -18 in the Northeast and Midwest regions, while in the North, South and Southeast regions, HPV-18 appears as the second most prevalent type [45][46][47][48]. This clearly shows that there is a need to develop a second generation of prophylactic vaccines against HPV, with a larger spectrum of action [49].…”

Section: A Pan-hpv Vaccinementioning

confidence: 99%

Vaccine Strategies against Human Papillomavirus: A Discussion Focused on Developing Countries

Freitas¹

2012

J Clin Cell Immunol

View full text Add to dashboard Cite

Cervical cancer is the second most common form of cancer among women, and responsible for 274,000 deaths each year, most of which occur in developing countries. Persistent infection with high-risk human papillomavirus (HR-HPV) is an essential factor in the development of cervical cancer and also a contributory factor in other types of cancer. The current prophylactic HPV vaccines provide protection against the -16 and -18 genotypes which are most commonly associated with cervical cancer worldwide. However, the increased costs of these vaccines inhibit their implementation in developing countries, affecting their viability. Moreover, a therapeutic vaccine is needed for women who are already infected by HPV and/or affected by HPV-related cancer. A number of innovative approaches to combat and treat HPV infection are currently being studied and some of these will be consider in this work, together with the development of new vaccines, especially in seriously affected areas located in developing countries. At the same time, there will be a discussion of the issues involved in carrying out effective HPV vaccination programs; these will take account of financial constraints, the lack of adequate infrastructure and the competing priorities, that are found in the surrounding social context of the developing countries.

show abstract

“…Some studies have already shown the immunogenic potential of the L2 protein against papillomavirus infections, identifying neutralizing and tumor rejection epitopes. However, the main advantage of a vaccine using the L2 gene is the potential to induce a broad spectrum of neutralizing antibodies, possibly with immune cross-reactivity, i.e., L2 can confer immune protection against a range of papillomaviruses, including HPV (Karanam et al, 2009;Jagu et al, 2011). In the case of E5, the possibility of using the gene as a therapeutic vaccine against papillomavirus is still underexplored.…”

Section: Resultsmentioning

confidence: 99%

“…L2 protein is the minor viral capsid protein but is essential for papillomavirus infection. It is responsible for binding to a secondary viral receptor, thereby facilitating the exit from the endosome and the delivery of the viral genome to the nucleus (Karanam et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

Short Communication Development of a DNA-based vaccine strategy against bovine papillomavirus infection, involving the E5 or L2 gene

et al. 2014

View full text Add to dashboard Cite

ABSTRACT. Papillomaviruses are known to cause tumor lesions, generally benign, in epithelial tissues of diverse organisms; these lesions may progress to cancer under suitable conditions. Bovine papillomavirus (BPV) can cause urinary bladder cancer and cancer of the upper gastrointestinal tract. Furthermore, BPV1 and BPV2 are implicated in the development of tumors in equids. Many studies with animal models clearly demonstrate that DNA vaccines are very effective tools in controlling viral infections, providing strong humoral and cellular immune responses. In this study, we have described the development of two vaccine constructs for the control of diseases caused by BPV. The 1st strategy is prophylactic and is based on the L2 gene; the 2nd is therapeutic and is based on the E5 gene. Vaccine constructs were obtained and evaluated in vitro in mammalian cells. The results show the occurrence of E5 and L2 transcription and viral protein production. These results confirm the functionality of the vaccine constructs in mammalian cells. This is the 1st step in the development of a DNA-based vaccine strategy for the control and/or treatment of diseases caused by BPV.

show abstract

Developing vaccines against minor capsid antigen L2 to prevent papillomavirus infection

Cited by 63 publications

References 128 publications

Papillomavirus Infection Requires γ Secretase

Papillomavirus Infection Requires γ Secretase

Vaccine Strategies against Human Papillomavirus: A Discussion Focused on Developing Countries

Short Communication Development of a DNA-based vaccine strategy against bovine papillomavirus infection, involving the E5 or L2 gene

Contact Info

Product

Resources

About