Conformation of the VP2 protein of bluetongue virus (BTV) determines the involvement in virus neutralization of highly conserved epitopes within the BTV serogroup.

نویسندگان

  • J R White
  • B T Eaton
چکیده

Seven neutralizing monoclonal antibodies (N-MAbs) were generated to an Australian isolate of bluetongue virus serotype 1 [BTV-1 (Aust)]. At least five of the N-MAbs were specific for epitopes on the outer coat protein VP2 and one was capable of binding SDS-treated protein in a Western blot. Six of the N-MAb panel bound and four of these neutralized BTV-1 (South Africa). None of the N-MAbs neutralized other Australian or South African BTV serotypes. However four of the N-MAb panel bound to a majority and two others bound with varying efficiency, to a more restricted but significant number of heterologous serotypes. Thus epitopes involved in the definition of one BTV serotype may be preserved on other serotypes but not be involved in their neutralization. To investigate the association between these epitopes and factors governing their expression, pools of neutralization-escape variants of BTV-1 (Aust), selected using each of six N-MAbs, were tested in virus neutralization and ELISA binding assays against the N-MAb panel. Each N-MAb displayed a unique reaction pattern with all 25 variants tested. All variants except one showed resistance to neutralization and/or reduced binding with at least three heterologous N-MAbs indicating the N-MAb-defined epitopes were mutually interactive. All 25 variants demonstrated increased resistance to neutralization by a bovine antiserum to BTV-1 (Aust). In total, the results from the variants revealed that the N-MAbs define seven distinct, interdependent neutralization epitopes which form at least part of a major neutralization domain on BTV. A majority of variants bound at least four and up to six N-MAbs, yet still resisted neutralization by them. This observation and the reaction of N-MAbs with BTV-1 (South Africa) and heterologous serotypes suggested that the conformation of the VP2 protein determines whether epitopes, conserved within the BTV serogroup, are involved in neutralization of individual serotypes of the virus.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Bluetongue virus serotype 17 sequence variation associated with neutralization.

Bluetongue virus (BTV) is an insect-transmitted orbivirus of importance to the cattle and sheep industry. The VP2 protein, encoded by L2, contains neutralizing epitopes. Previously, a panel of neutralizing monoclonal antibodies (MAbs) to the BTV serotype 17 (BTV-17) prototype strain was generated and it was determined that the neutralization domain consists of three overlapping epitopes. Over 3...

متن کامل

Bluetongue virus replication, molecular and structural biology.

The icosahedral bluetongue virus (BTV) particle (~80 nm diameter) is composed of three distinct protein layers. These include the subcore shell (VP3), core-surface layer (VP7) and outer capsid layer (VP2 and VP5). The core also contains ten dsRNA genome segments and three minor proteins (VP1[Pol], VP4[CaP]and VP6[Hel]), which form transcriptase complexes. The atomic structure of the BTV core ha...

متن کامل

Restriction analysis of conserved and variable regions of VP2 gene of Indian isolates of bluetongue virus serotype 1.

Bluetongue virus (BTV) is a member of Orbivirus genus in family Reoviridae. The virus genome is composed of 10 double-stranded RNA segments. The RNA segment L2 encodes an outer capsid viral protein VP2, which is the main determinant of neutralization and serotype-specific immune response. BTV serotype 1 (BTV-1) specific novel primer pair was designed using VP2 gene sequences available in GenBan...

متن کامل

Genetic Characterization of Toggenburg Orbivirus, a New Bluetongue Virus, from Goats, Switzerland

A novel bluetongue virus (BTV) termed Toggenburg orbivirus (TOV) was detected in goats from Switzerland by using real-time reverse transcription-PCR. cDNA corresponding to the complete sequence of 7 of 10 double-stranded RNA segments of the viral genome was amplified by PCR and cloned into a plasmid vector. Five clones for each genome segment were sequenced to determine a consensus sequence. BL...

متن کامل

Analysis and phylogenetic comparisons of full-length VP2 genes of the 24 bluetongue virus serotypes.

The outer capsid protein VP2 of Bluetongue virus (BTV) is a target for the protective immune response generated by the mammalian host. VP2 contains the majority of epitopes that are recognized by neutralizing antibodies and is therefore also the primary determinant of BTV serotype. Full-length cDNA copies of genome segment 2 (Seg-2, which encodes VP2) from the reference strains of each of the 2...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • The Journal of general virology

دوره 71 ( Pt 6)  شماره 

صفحات  -

تاریخ انتشار 1990