L1 codes the major capsid L1 protein Human papillomavirus type 16. The papillomavirus major capsid protein coded by L1, is a ~55 kD protein capable of self-assembling into virus-like particles (VLPs) spontaneously. It has been reported that purified recombinant L1 proteins can achieve this complex assembly reaction without the help of any chaperones(Fig. 1.).
Fig. 1. Structure of an L1 capsomer. (Christopher et al, 2013)
L1 is a commonly researched project in that the efficient bivalent vaccine consisting of recombinant L1 proteins from HPV-16 and -18, had been used to prevent cervical cancer. L1 is responsible for causing high-titre neutralizing antibodies, since specific loop structures of the L1 protein on the surface of pentamers contain hypervariable immune-dominant regions. Thus the generation of neutralizing antibodies with different binding affinities is likely due to the polymorphism of the above mentioned loops.
Moreover, given that the entire exterior surface of the stabilized mature virion comes from L1, it is apparent that the initial attachment to host tissues or cells, along with the ultimate release of the viral genome into a new host cell after original attachment to cells must be able to be carried out by L1. One distinctive feature of the virion is knobby, with each of the 72 knobs being composed of a pentameric L1 capsomer. Forming the floor between the capsomer knobs are the N- and C-termini of L1 that are arranged as extended “invading arms”. The C-terminus of L1 is especially elaborate and its invading arm wraps up the canyon-facing surface of the invaded capsomer to a point near the outer apex of the knob. An inter-L1 disulfide bond is formed between the neighboring capsomers at the high apical point.
One major application of L1 is that it has been actively and effectively used in vaccination against the cervical cancer. However, it has also been suggested that changes in HPV-16 and -18 virus population could be produced through long-term vaccination, which hinders the effect of vaccination. In a related study, 10 HPV16 FG loop L1 protein mutants have been generated by researchers and their ability to self-assemble into VLP, along with their immunogenicity, and their ability to transduce cells when used as pseudovirions were also analyzed. Results reveal that the majority of the mutants had lost their ability to transduce cells with only one exception, the two chimeric HPV16/31 L1 protein FG loop mutants. Sera from mice that are immunized with HPV16 L1 wt VLPs very weakly neutralized pseudovirions derived from these two HPV16/31 L1 protein FG loop mutants, suggesting that only a few point compositions within the FG loop are enough to generate a new serotype capable of escaping vaccination.
Moreover, infection with different species of cutaneous human papillomaviruses belonging to the genus alpha (cαHPVs) and associated skin disease are highly prevalent in organ transplant recipients, emphasizing the importance of the immunological control of HPV infection. The systemic humoral immune response against cαHPV could be used to reflect the individual degree of iatrogenic immunosuppression, which indicated a higher probability of cαHPV infection among OTR(open translation frame ), especially during the early phase after organ transplantation.
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