Zach Walker & Alainna Conroy

 

Virus: Varicella zoster virus

Disease: Chickenpox/ Shingles

 

Welcome to today’s episode of Genomics Revolution. I am Zach Walker and am here with Alainna Conroy and we will be discussing the varicella zoster virus. We will be referring to this as the VZV.  

 

BACKGROUND/ DISCOVERY:

In 1888, Von Bokay first observed that the VZV was related herpes zoster virus or shingles when children contracted VZV from adults who had shingles. Then in 1954, Thomas Weller took cell cultures from VZV lesions to scientifically distinguish VZV from shingles. After this in the 1970s, Japan developed the Oka strain of the varicella vaccine.

 

WHY WE CARE:

VZV causes chickenpox or shingles. Chicken pox results from initial infection of the VZV and occurs in children. The VZV can remain silenced in individuals and become activated later in life resulting in shingles. 

 

GENOME: 

VZV is a member of the varicellovirus genus and belongs to the alpha-herpesvirus family. The VZV genome has at least 70 genes, most of them homologs in herpes simplex virus. 

 

In 1986, the complete sequence of the VZV genome was determined by Davison and Scott. They determined the genome is variable in size, but the sequence they looked at was 124, 884 base pairs and contained 70 genes between 2 strands of DNA. The VZV genome encodes at least 71 unique proteins. The sequence is linear with a single unpaired nucleotide on each end. These will pair together and become circular in cells that are infected with the virus. 

 

FINDINGS FROM SEQUENCING

After sequencing the VZV genome, Davidson and Scott determined that there are a lot fewer repeats among the sequence compared to HSV-1 and the places with repeats are unrelated to HSV-1. The research describe these repeats as accumulated parasitic sequences that possibly happen through recombination, in regions that they do not cause a selective disadvantage. This affects the size of some of the encoded proteins and could have a role in different functions of these genes. 

 

By looking at the sequence and determining the gene layout, Davidson and Scott were able to determine that both the VZV and HSV-1 have similar gene layouts. Many of the genes encode similar proteins with specific properties. Research reports that there are also a limited amount of regions with significant differences. This indicates that the proteins are highly conserved and can be determined that the functions of VZV and HSV-1 are very similar. 

 

In a study done by Argaw et al, they were able to determine distinguishing parts in the nucleotide sequence between the originally sequenced VZV and the VZV Oka vaccine strain. They looked at about 34,000 from the 3’ end, they were able to see numerous changes that they describe as “nonconservative amino acid substitutions in coding sequences for virus gene products” (1154). The biggest change occurred in ORF62 where a glycine was substituted for an arginine leading to a cleave site. The study reports that mutations in ORF62 may factor into attenuation of the Oka vaccine strain. There is also a nucleotide insertions that allow a distinction.

 

Another finding by Lebrun et al is that ORF9p binds to the adaptor protein complex 1 also known as AP-1. AP-1 is involved in the intra-cellular transport and moving proteins between endosomes and the trans-Golgi network. With this interaction between ORF9p and AP-1 it allows the secondary envelopment of VZV. However, in the same study conducted by Lebrun et al they were able to determine that leucine 231 is conserved among alphahepresviruses and was critical in interaction between ORF9p and AP-1. To help show this,  they mutated leucine 231 to alanine in ORF9p and found that by mutating leucine 231 to alanine it strongly impaired the viral growth of VZV.

 

This ends today’s episode of Genomics Revolution, thank you for your time and we hope you were able to learn something new!

 

 

Works Cited:
Argaw, T., Cohen, J. I., Klutch, M., Lekstrom, K., Yoshikawa, T., Asano, Y., Krause, P. R. (2000) Nucleotide sequences that distinguish Oka vaccine from parental Oka and other Varicella-Zoster Virus isolates. The Journal of Infections Diseases, 181, 1153-1157. 

 

Centers for Disease Control and Prevention, “Varicella” wonder.cdc.gov/wonder/prevguid/p0000108/p0000108.asp

 

Cohen, J. I., The Varicella-Zoster Virus Genome. Curr Top Microbiol Immunol., 342, 1-14. 

 

Davison, A. J., Scott J. E. (1986). The complete DNA sequence of Varicella-Zoster Virus. J. Gen. Virol. 67, 1759-1816. 

 

Lebrun, M., Lambert, J., Riva, L., Thelen, N., Rambout, X., Blondeau, C., Thiry, M., Snoeck, R., Twizere, JC., Dequiedt, F., Andrei, G., Sadzot-Delvaux, C. (2018) Varicella-Zoster Virus ORF9p Binding to Cellular Adaptor Protein Complex 1 Is Important for Viral Infectivity. J Virol. 92, 1-22