Sequence analysis and structural implications of rotavirus capsid proteins

Abstract

Rotavirus is the major cause of severe virus-associated gastroenteritis worldwide in children aged 5 and younger. Many children lose their lives annually due to this infection and the impact is particularly pronounced in developing countries. The mature rotavirus is a non-enveloped triple-layered nucleocapsid containing 11 double stranded RNA segments. Here a global view on the sequence and structure of the three main capsid proteins, VP2, VP6 and VP7 is shown by generating a consensus sequence for each of these rotavirus proteins, for each species obtained from published data of representative rotavirus genotypes from across the world and across species. Degree of conservation between species was represented on homology models for each of the proteins. VP7 shows the highest level of variation with 14-45 amino acids showing conservation of less than 60%. These changes are localised to the outer surface alluding to a possible mechanism in evading the immune system. The middle layer, VP6 shows lower variability with only 14-32 sites having lower than 70% conservation. The inner structural layer made up of VP2 showed the lowest variability with only 1-16 sites having less than 70% conservation across species. The results correlate with each protein's multiple structural roles in the infection cycle. Thus, although the nucleotide sequences vary due to the error-prone nature of replication and lack of proof reading, the corresponding amino acid sequence of VP2, 6 and 7 remain relatively conserved. Benefits of this knowledge about the conservation include the ability to target proteins at sites that cannot undergo mutational changes without influencing viral fitness; as well as possibility to study systems that are highly evolved for structure and function in order to determine how to generate and manipulate such systems for use in various biotechnological applications.

A Recombinant Rotavirus Antigen Based on the Coat Protein of Alternanthera Mosaic Virus

“…This epitope was reported to induce a strong protective immune response, comparable to that observed for immunization with fullsize VP6, in mice [7]. This fragment is conserved in a number of group A strains [6] and can be considered a promising antigenic determinant for development of vaccines against rotavirus infection.…”

“…The major rotavirus antigens are VP6, VP7, VP5*, and VP8*. The available data indicate that the structural protein VP6 is highly conserved: 87% of its amino acid sequence is invariable in group A strains [6]. VP6 plays a central role in the development of the specific immune response: the major antibodies produced in response to a natural rotavirus infection are specific to VP6.…”

Новый Подход К Разработке Кандидатной Вакцины Против Ротавируса На Основе Двух Вирусов Растений

“…Основными антигенами ротавируса считаются структурные белки VP6 (из него состоит промежуточный капсид) (11,13,14), VP7 (образует внешний капсид) (13,15), VP4 (формирует шипы) (15,16) и продукты протеолиза последнего -VP5* и VP8* (17). VP6 консервативен для штаммов группы А (11,18), вызывающих заболевания человека, и играет ключевую роль в формировании протективного иммунного ответа, несмотря на то, что не находится на поверхности вириона. Белок VP6 способен вызывать практически 100 % защиту против ротавируса у мышей уже после первой иммунизации (11).…”

“…Однако известно, что индивидуальные белки даже большей молекулярной массы сами по себе зачастую низкоиммуногенны, и использование какого-либо адъюванта необходимо для формирования эффективного иммунного ответа. В частности, в литературе описано крити-ческое значение адъюванта для создания протективного иммунитета химерным белком, который представляет собой белок VP6 ротавируса, слитый с мальтоза-связывающим белком (maltose-binding protein), и имеет молекулярную массу почти 88 кДа (18,19,37).…”