scholarly journals Functional Dissection of the Dominant Role of CD55 in Protecting Vesicular Stomatitis Virus against Complement-Mediated Neutralization

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 373
Author(s):  
Nisha Asok Kumar ◽  
Sreenath Muraleedharan Suma ◽  
Umerali Kunnakkadan ◽  
Joydeep Nag ◽  
Reshma Koolaparambil Mukesh ◽  
...  

The human complement system is an important part of the innate immune system. Its effector pathways largely mediate virus neutralization. Vesicular stomatitis virus (VSV) activates the classical pathway of the complement, leading to virus neutralization by lysis. Two host-derived membrane-associated regulators of complement activation (RCA), CD55 and CD46, which are incorporated into the VSV envelope during egress, confer protection by delaying/resisting complement-mediated neutralization. We showed previously that CD55 is more effective than CD46 in the inhibition of neutralization. In this study, we identified that, at the protein level, VSV infection resulted in the down-regulation of CD46 but not CD55. The mRNA of both the RCAs was significantly down-regulated by VSV, but it was delayed in the case of CD55. The immunoblot analysis of the levels of RCAs in the progeny virion harvested at three specific time intervals, points to an equal ratio of its distribution relative to viral proteins. Besides reconfirming the dominant role of CD55 over CD46 in shielding VSV from complement, our results also highlight the importance of the subtle modulation in the expression pattern of RCAs in a system naturally expressing them.

1990 ◽  
Vol 64 (4) ◽  
pp. 1716-1725 ◽  
Author(s):  
D Blondel ◽  
G G Harmison ◽  
M Schubert

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 108
Author(s):  
Victor Latorre ◽  
Ron Geller

The viral order Mononegavirales consist of eight virus families. Members of these families include some of the most infectious (Measles, lethal (Ebola and Rabies), and most common viruses (Respiratory syncytial virus, RSV). Despite their medical importance, few vaccines and no antiviral treatments are available for treating infections with these viruses. Being obligate cellular parasites, viruses must rely on the cellular machinery for their replication. One example of this is the widespread use of molecular chaperones, which assist the correct folding of newly synthesized proteins, refold misfolded or aggregated proteins, and play key roles in maintaining proteostasis in cells. Targeting chaperones required for viral replication may, therefore, provide an antiviral approach. In this work, we set out to identify all the members of the cytoplasmic chaperone network that are involved in the replication of RSV using an RNA interference screen. Among our hits is valosin-containing protein (VCP; also known as p97), a chaperone involved in ubiquitin-mediated protein degradation, which has been shown to play a role in the life cycle of several viruses. We investigated the role of VCP during RSV and vesicular stomatitis virus (VSV) infections using specific VCP inhibitors. Our results suggest that VCP activity is necessary for RSV and VSV replication and may constitute a promising antiviral approach for the Mononegavirales.


Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 386 ◽  
Author(s):  
Ferdinand Zettl ◽  
Toni Luise Meister ◽  
Tanja Vollmer ◽  
Bastian Fischer ◽  
Jörg Steinmann ◽  
...  

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2, a new member of the genus Betacoronavirus, is a pandemic virus, which has caused numerous fatalities, particularly in the elderly and persons with underlying morbidities. At present, there are no approved vaccines nor antiviral therapies available. The detection and quantification of SARS-CoV-2-neutralizing antibodies plays a crucial role in the assessment of the immune status of convalescent COVID-19 patients, evaluation of recombinant therapeutic antibodies, and the evaluation of novel vaccines. To detect SARS-CoV-2-neutralizing antibodies, classically, a virus-neutralization test has to be performed at biosafety level 3, considerably limiting the general use of this test. In the present work, a biosafety level 1 pseudotype virus assay based on a propagation-incompetent vesicular stomatitis virus (VSV) has been used to determine the neutralizing antibody titers in convalescent COVID-19 patients. The neutralization titers in serum of two independently analyzed patient cohorts were available within 18 h and correlated well with those obtained with a classical SARS-CoV-2 neutralization test (Pearson correlation coefficients of r = 0.929 and r = 0.939, respectively). Most convalescent COVID-19 patients had only low titers of neutralizing antibodies (ND50 < 320). The sera of convalescent COVID-19 patients also neutralized pseudotype virus displaying the SARS-CoV-1 spike protein on their surface, which is homologous to the SARS-CoV-2 spike protein. In summary, we report a robust virus-neutralization assay, which can be used at low biosafety level 1 to rapidly quantify SARS-CoV-2-neutralizing antibodies in convalescent COVID-19 patients and vaccinated individuals.


2019 ◽  
Vol 40 (6Supl3) ◽  
pp. 3769
Author(s):  
Camila de Sousa Bezerra ◽  
Jéssica Tatiane Sauthier ◽  
Juliana Felipetto Cargnelutti ◽  
Gisele Cândida Ramalho ◽  
Denise Batista Nogueira ◽  
...  

This study aimed to determine the prevalence of vesicular stomatitis virus (VSV) in buffaloes in the state of Paraíba, Northeastern Brazil. The study was carried out in 14 herds in the municipalities of Alagoa Nova, Areia, Campina Grande, Guarabira, Juripiranga, Santa Helena, Sapê, Rio Tinto, Santana dos Garrotes, Itatuba, Solânea, and Cacimbas. The studied population was formed by buffalo females reared for meat and milk, comprising of mixed and Murrah breeds, at least 24 months of age. For the serological diagnosis of VSIV-3, the virus-neutralization test (VN) was performed, using the VSIV-3 isolate 2013 São Bento/Paraíba. Real prevalence was 2.6% for VSIV-3, with antibody titers ranging from 160 to 1280. This is the first study to characterize VSV circulation in the buffalo population in Northeastern Brazil, where infection is considered endemic; some aspects of virus maintenance are not fully understood, such as the role of reservoirs in endemic areas. The identification of seroreactive animals in this study demonstrates the circulation of VSIV-3 in the buffalo species. Reports of virus isolation in this species have not yet been described, which suggests the need for investigating the role of buffaloes in vesicular stomatitis epidemiology.


1996 ◽  
Vol 135 (1) ◽  
pp. 153-167 ◽  
Author(s):  
J Peränen ◽  
P Auvinen ◽  
H Virta ◽  
R Wepf ◽  
K Simons

Rab8 is a small Ras-like GTPase that regulates polarized membrane transport to the basolateral membrane in epithelial cells and to the dendrites in neurons. It has recently been demonstrated that fibroblasts sort newly synthesized proteins into two different pathways for delivery to the cell surface that are equivalent to the apical and the basolateral post-Golgi routes in epithelial cells (Yoshimori, T., P. Keller, M.G. Roth, and K. Simons. 1996. J. Cell Biol. 133:247-256). To determine the role of Rab8 in fibroblasts, we used both transient expression systems and stable cell lines expressing mutant or wild-type (wt) Rab8. A dramatic change in cell morphology occurred in BHK cells expressing both the wt Rab8 and the activated form of the GTPase, the Rab8Q67L mutant. These cells formed processes as a result of a reorganization of both their actin filaments and microtubules. Newly synthesized vesicular stomatitis virus G glycoprotein, a basolateral marker protein in MDCK cells, was preferentially delivered into these cell outgrowths. Based on these findings, we propose that Rab8 provides a link between the machinery responsible for the formation of cell protrusions and polarized biosynthetic membrane traffic.


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