Switch from Polymorphic to Homogenous Self‐Assembly of Virus‐Like Particles of Simian Virus 40 through Double‐Cysteine Substitution

Small ◽  
2020 ◽  
Vol 16 (45) ◽  
pp. 2004484
Author(s):  
Chengchen Xu ◽  
Weiwei Zhu ◽  
Hanjing Mao ◽  
Wenjing Zhang ◽  
Gen‐Quan Yin ◽  
...  
Small ◽  
2020 ◽  
Vol 16 (45) ◽  
pp. 2070248
Author(s):  
Chengchen Xu ◽  
Weiwei Zhu ◽  
Hanjing Mao ◽  
Wenjing Zhang ◽  
Gen‐Quan Yin ◽  
...  

2020 ◽  
Vol 6 (16) ◽  
pp. eaaz1639 ◽  
Author(s):  
Mariska G. M. van Rosmalen ◽  
Douwe Kamsma ◽  
Andreas S. Biebricher ◽  
Chenglei Li ◽  
Adam Zlotnick ◽  
...  

Many viruses use their genome as template for self-assembly into an infectious particle. However, this reaction remains elusive because of the transient nature of intermediate structures. To elucidate this process, optical tweezers and acoustic force spectroscopy are used to follow viral assembly in real time. Using Simian virus 40 (SV40) virus-like particles as model system, we reveal a multistep assembly mechanism. Initially, binding of VP1 pentamers to DNA leads to a significantly decreased persistence length. Moreover, the pentamers seem able to stabilize DNA loops. Next, formation of interpentamer interactions results in intermediate structures with reduced contour length. These structures stabilize into objects that permanently decrease the contour length to a degree consistent with DNA compaction in wild-type SV40. These data indicate that a multistep mechanism leads to fully assembled cross-linked SV40 particles. SV40 is studied as drug delivery system. Our insights can help optimize packaging of therapeutic agents in these particles.


2005 ◽  
Vol 86 (6) ◽  
pp. 1703-1708 ◽  
Author(s):  
Annika Lundstig ◽  
Linda Eliasson ◽  
Matti Lehtinen ◽  
Kestutis Sasnauskas ◽  
Pentti Koskela ◽  
...  

Possible human infection with simian virus 40 (SV40) has been of great concern ever since SV40 was discovered in polio vaccines. Human populations are SV40-seropositive, but because of serological cross-reactivity between SV40 and the human polyomaviruses BK virus (BKV) and JC virus (JCV), it is debatable whether these antibodies are specific. An SV40-specific serological assay was established, based on purified virus-like particles (VLPs), where the SV40 VLPs were blocked with hyperimmune sera to BKV and JCV. Competition with SV40 hyperimmune sera was used as a confirmatory test. Among 288 Swedish children of between 1 and 13 years of age, 7·6 % had SV40-specific antibodies. SV40 seroprevalence reached a peak of 14 % at 7–9 years of age. Among 100 control patients with benign tumours, 9 % were SV40-seropositive. However, SV40 DNA was not detectable in corresponding buffy-coat samples. In serial samples taken up to 5 years apart from 141 Finnish women participating in the population-based serological screening for congenital infections, only two of 141 women were SV40-seropositive in both samples. Six women seroconverted and eight women had a loss of antibodies over time. None of the SV40-seropositive samples contained detectable SV40 DNA. In conclusion, there is a low prevalence of SV40-specific antibodies in the Nordic population. The SV40 antibodies appear to have a low stability over time and their origin is not clear.


2004 ◽  
Vol 78 (2) ◽  
pp. 930-937 ◽  
Author(s):  
Reimar Johne ◽  
Hermann Müller

ABSTRACT Virions of polyomaviruses consist of the major structural protein VP1, the minor structural proteins VP2 and VP3, and the viral genome associated with histones. An additional structural protein, VP4, is present in avian polyomavirus (APV) particles. As it had been reported that expression of APV VP1 in insect cells did not result in the formation of virus-like particles (VLP), the prerequisites for particle formation were analyzed. To this end, recombinant influenza viruses were created to (co)express the structural proteins of APV in chicken embryo cells, permissive for APV replication. VP1 expressed individually or coexpressed with VP4 did not result in VLP formation; both proteins (co)localized in the cytoplasm. Transport of VP1, or the VP1-VP4 complex, into the nucleus was facilitated by the coexpression of VP3 and resulted in the formation of VLP. Accordingly, a mutant APV VP1 carrying the N-terminal nuclear localization signal of simian virus 40 VP1 was transported to the nucleus and assembled into VLP. These results support a model of APV capsid assembly in which complexes of the structural proteins VP1, VP3 (or VP2), and VP4, formed within the cytoplasm, are transported to the nucleus using the nuclear localization signal of VP3 (or VP2); there, capsid formation is induced by the nuclear environment.


Nano Letters ◽  
2016 ◽  
Vol 16 (10) ◽  
pp. 6164-6171 ◽  
Author(s):  
Xianxun Sun ◽  
Wei Li ◽  
Xiaowei Zhang ◽  
Mi Qi ◽  
Zhiping Zhang ◽  
...  

2012 ◽  
Vol 93 (12) ◽  
pp. 2658-2667 ◽  
Author(s):  
Anja Zielonka ◽  
Alma Gedvilaite ◽  
Jochen Reetz ◽  
Uwe Rösler ◽  
Hermann Müller ◽  
...  

Polyomaviruses are aetiological agents of fatal acute diseases in various bird species. Genomic analysis revealed that avian polyomavirus (APyV), crow polyomavirus (CPyV), finch polyomavirus (FPyV) and goose hemorrhagic polyomavirus (GHPyV) are closely related to each other, but nevertheless form separate viral species; however, their serological relationship was previously unknown. As only APyV can be grown efficiently in tissue culture, virus-like particles (VLPs) were generated by expression of the genomic regions encoding the major structural protein VP1 of these viruses in yeast; these were used to elicit type-specific antibodies in rabbits and as antigens in serological reactions. For increased VLP assembly, a nuclear-localization signal was introduced into APyV-VP1. VLPs derived from the VP1 of the monkey polyomavirus simian virus 40 served as control. APyV-, GHPyV- and CPyV-VLPs showed haemagglutinating activity with chicken and human erythrocytes. CPyV- and GHPyV-specific sera showed slight cross-reactions in immunoblotting, haemagglutination-inhibition assay and indirect ELISA. The FPyV-specific serum inhibited the haemagglutination activity of APyV-VLPs slightly and showed a weak cross-neutralizing activity against APyV in cell-culture tests. Generally, these data indicate that the four polyomaviruses of birds are serologically distinct. However, in accordance with genetic data, a relationship between CPyV and GHPyV as well as between APyV and FPyV is evident, and grouping into two different serogroups may be suggested. The haemagglutinating activity of APyV, CPyV and GHPyV may indicate similar receptor-binding mechanisms for these viruses. Our data could be useful for the development of vaccines against the polyomavirus-induced diseases in birds and for interpretation of diagnostic test results.


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