Some Observations on Neurotropic Effects of Vesicular Stomatitis Virus in the Mouse Brain (Part 3 of 3)

1962 ◽  
Vol 22 (2) ◽  
pp. 103-120
Author(s):  
Hartwig Kuhlenbeck ◽  
Maria Wiener Kirber
Keyword(s):  
Mouse Brain ◽  
Vesicular Stomatitis Virus ◽  
Vesicular Stomatitis ◽  
Neurotropic Effects ◽  
Brain Part

scholarly journals Chikungunya, Influenza, Nipah, and Semliki Forest Chimeric Viruses with Vesicular Stomatitis Virus: Actions in the Brain

2017 ◽  
Vol 91 (6) ◽  
Author(s):  
Anthony N. van den Pol ◽  
Guochao Mao ◽  
Anasuya Chattopadhyay ◽  
John K. Rose ◽  
John N. Davis
Keyword(s):  
Mouse Brain ◽  
Vesicular Stomatitis Virus ◽  
Adult Mouse ◽  
Semliki Forest Virus ◽  
Adult Brain ◽  
Adult Mouse Brain ◽  
Glycoprotein Gene ◽  
Vesicular Stomatitis ◽  
The Brain ◽  
Chimeric Viruses

ABSTRACT Recombinant vesicular stomatitis virus (VSV)-based chimeric viruses that include genes from other viruses show promise as vaccines and oncolytic viruses. However, the critical safety concern is the neurotropic nature conveyed by the VSV glycoprotein. VSVs that include the VSV glycoprotein (G) gene, even in most recombinant attenuated strains, can still show substantial adverse or lethal actions in the brain. Here, we test 4 chimeric viruses in the brain, including those in which glycoprotein genes from Nipah, chikungunya (CHIKV), and influenza H5N1 viruses were substituted for the VSV glycoprotein gene. We also test a virus-like vesicle (VLV) in which the VSV glycoprotein gene is expressed from a replicon encoding the nonstructural proteins of Semliki Forest virus. VSVΔG-CHIKV, VSVΔG-H5N1, and VLV were all safe in the adult mouse brain, as were VSVΔG viruses expressing either the Nipah F or G glycoprotein. In contrast, a complementing pair of VSVΔG viruses expressing Nipah G and F glycoproteins were lethal within the brain within a surprisingly short time frame of 2 days. Intranasal inoculation in postnatal day 14 mice with VSVΔG-CHIKV or VLV evoked no adverse response, whereas VSVΔG-H5N1 by this route was lethal in most mice. A key immune mechanism underlying the safety of VSVΔG-CHIKV, VSVΔG-H5N1, and VLV in the adult brain was the type I interferon response; all three viruses were lethal in the brains of adult mice lacking the interferon receptor, suggesting that the viruses can infect and replicate and spread in brain cells if not blocked by interferon-stimulated genes within the brain. IMPORTANCE Vesicular stomatitis virus (VSV) shows considerable promise both as a vaccine vector and as an oncolytic virus. The greatest limitation of VSV is that it is highly neurotropic and can be lethal within the brain. The neurotropism can be mostly attributed to the VSV G glycoprotein. Here, we test 4 chimeric viruses of VSV with glycoprotein genes from Nipah, chikungunya, and influenza viruses and nonstructural genes from Semliki Forest virus. Two of the four, VSVΔG-CHIKV and VLV, show substantially attenuated neurotropism and were safe in the healthy adult mouse brain. VSVΔG-H5N1 was safe in the adult brain but lethal in the younger brain. VSVΔG Nipah F+G was even more neurotropic than wild-type VSV, evoking a rapid lethal response in the adult brain. These results suggest that while chimeric VSVs show promise, each must be tested with both intranasal and intracranial administration to ensure the absence of lethal neurotropism.

626: Initial Experience with Vesicular Stomatitis Virus as a Treatment for Bladder Cancer

2006 ◽  
Vol 175 (4S) ◽  
pp. 202-202
Author(s):  
Sherwin Zargaroff ◽  
Yuancheng Wang ◽  
Xiayong Zheng ◽  
Jian Pu ◽  
Savio L. Woo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Vesicular Stomatitis Virus ◽  
Initial Experience ◽  
Vesicular Stomatitis

Inhibition of Various Steps in the Replication Cycle of Vesicular Stomatitis Virus Contributes to Its Photoinactivation by AlPcS4 or Pc4 and Red Light

1999 ◽  
Vol 69 (3) ◽  
pp. 353 ◽  
Author(s):  
Anne C. E. Moor ◽  
Angeline E. Wagenaars-van Gompel ◽  
Ralph C. A. Hermanns ◽  
Jannes van der Meulen ◽  
Jolanda Smit ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Red Light ◽  
Replication Cycle ◽  
Vesicular Stomatitis
Sign in / Sign up

Export Citation Format

Share Document