Sunday, April 18, 2010

Viruses: Capsid Structure

Hi Lisa,

Sorry it took me so long to respond to your last post. I just keep getting so bogged down in school work…You are correct in stating that some people call the panleukopenia vaccination or FVRCP vaccination the distemper vaccination, however people who refer to this vaccination (FVRCP) as a distemper vaccination are mistaken and need to be and should be corrected by vets who know better than to call panleukopenia, distemper. As I previously mentioned, Panleukopenia is an altogether different virus from distemper.
To refresh everyone’s memory, the panleukopenia virus is a member of the parvoviridae family of viruses and belongs to the parvovirus genus. The distemper virus is a member of the paramyxoviridae family of viruses and belongs to the morbillivirus genus. Panleukopenia is a ssDNA (single stranded DNA) virus, where as distemper is an ssRNA (single stranded RNA) virus.

To help illustrate the differences in these two viruses, I think it might be useful to show and explain a little bit about virus packaging, so here is a great insert from one of my Virology textbooks:

“Outside of their host cells, viruses survive as virus particles, also known as virions. The virion is a gene delivery system; it contains the virus genome (for those of you who are uncertain as to what a genome actually is, it is an organism’s complete set of hereditary information, including all of its genes. It is encoded either in DNA, or for many types of viruses RNA. Basically the genome contains all the information needed to build and maintain that organism…) and it’s (the virions) functions are to protect the genome and to aid its entry into a host cell, where it can be replicated and packaged into new virions. [In viruses] the genome is packaged in a protein structure known as a capsid.”
There are four categories of genomes: dsDNA (double stranded DNA), ssDNA (single stranded DNA), dsRNA (double stranded RNA), and ssRNA (single stranded RNA). As was noted above, Panleukopenia is a ssDNA virus where as Distemper is an ssRNA virus. Now as for the FVRCP vaccination, you are correct in stating that the vaccination contains Rhinotracheitis, Calicivirus and Panleukopenia. Below are some illustrations of the Rhinotracheitis, Calicivirus and Panleukopenia capsid structures:

If you look at each of the above illustrations carefully, you will notice that each of these viruses has an icosahedral symmetry. (You can think of these as looking similar to a soccer ball which has a spherical truncated iscosahedron symmetry.) Now I should explain that some viruses are enveloped viruses. An enveloped virion to keep things simple, is simply a virion which has fused with a portion of a cell's plasma membrane. The Rhinotracheitis virus is an example of an enveloped virus (look at the illustration above and you will notice that the green icosahedral capsid is enclosed/ enveloped by a larger circle,) as are many influenza viruses.
Now let's move on to the Distemper capsid structure shown below:

The distemper virus is an enveloped, spherical virus. It's capsid structure is competely different from that of Rhinotracheitis, Calicivirus and the Panleukopenia virus. It is spherical not icosahedral in nature. This capsid structure is not found in the FVRCP vaccination. In fact the distemper virus itself is not found in felines, to date there has never be a host range shift in the virus which would allow it to affect both canines and felines. The distemper virus does however affect the canine population. The vaccination for canine distemper, like FVRCP, is commonly packaged with other viruses, and is commonly know as a recombitek vaccination, which vaccinates canines against distemper, coronavirus, parvovirus, hepatitis, parainfluenza, leptospira canicola and leptospira icteroharmorraghiae.
Because the capsid structures of these viruses are different, so two is the viruses replication cycle (you can think of it as a reproductive cycle). Below you will find how each virus generally replicates itself:

Herpesviridae
REPLICATION
NUCLEAR

Lytic replication:

1.Virus attaches to host receptors through gB, gC, gD and gH .
2.Fusion with the plasma membrane to release the core and the tegument proteins into the host cytoplasm.
3.The capsid is transported to the nuclear pore where the viral DNA is released into the nucleus.
4.Transcription of immediate early genes which promote transcription of early genes.
5.Transcription of early viral mRNA by host polymerase II, transport into the cytoplasm and translation into early proteins.
6.Early proteins are involved in replication of the viral DNA and are transported back into the nucleus.
7.Synthesis of multiple copies of viral DNA by the viral DNA-dependent DNA polymerase.
8.Transcription of late mRNAs by host polymerase II, transport into the cytoplasm and translation into late proteins.
9.Late proteins are structural or core proteins and are transported back into the nucleus.
10.Assembly of the virus and budding through the inner lamella of the nuclear membrane which has been modified by the insertion of herpes glycoproteins, throughout the Golgi and final release at the plasma membrane.
Latent replication : replication of circular viral episome in tandem with the host cell DNA using the host cell replication machinery.

Calicivirus
REPLICATION

1.Virus attaches to host receptors and is internalized.
2.Uncoating, and release of the viral genomic RNA into the cytoplasm.
3.VPg is removed from the viral RNA, which is then translated into a processed ORF1 polyprotein to yield the mature non-structural proteins involved in RNA transcription.
4.Negative-sense complementary ssRNAs are synthesized using the genomic RNAs as a templates.
5.New genomic RNAs are synthesized using the negative-sense RNAs as templates.
6.Expression of sgRNA yields the basic protein (and capsid protein).
7.Assembly and release of new virions.

Panleukopenia
REPLICATION
NUCLEAR

1.Virus penetrates into the host cell.
2.Uncoating, and release of the viral genomic ssDNA into the nucleus.
3.The ssDNA is converted into dsDNA by cellular proteins.
4.viral mRNAs are transcribed when host cell enters S phase and translated to produce viral proteins.
5.Replication occurs through rolling-hairpin mechanism, whith NS1 nickase binding covalently to the 5’ genomic end.
6.Individual ssDNA genomes are excised from replication concatemers by a process called junction resolution.
7.These newly synthesized ssDNA can either
a) be converted to dsDNA and serve as a template for transcription/replication
b) be encapsidated to form new virions that can budd out of the host cell.

Canine Distemper
REPLICATION
CYTOPLASMIC

1.Virus attaches to host cell surface receptors through H glycoprotein.
2.Fusion with the plasma membrane; ribonucleocapsid is released in the cytoplasm.
3.sequential transcription, viral mRNAs are capped and polyadenylated in the cytoplasm.
4.Replication presumably starts when enough nucleoprotein is present to encapsidate neo-synthetized antigenomes and genomes.
5.the ribonucleocapsid interacts with the matrix protein under the plasma membrane and buds, releasing the virion.

Thus to wrap things up capsid structures provide us with key information about viruses. The larger a viruses capsid is, the more genetic information can be recorded/stored within it. On the other hand, the smaller a capsid is, the less information can be recorded/stored. This is key in understanding how viruses work, since viruses such as those belonging to the parvovirus genus, are smaller and are therefore more dependent upon a host's cell to provide information/genetic material needed in order for the virus to replication (reproduce itself).
I hope you can see now why calling an FVRCP vaccination a distemper vaccination is misleading. They are two completely different viruses, and their vaccinations accordingly are two totally different vaccinations for two completely different hosts (in this case animals). Therefore to put it in the most laymen of terms the FVRCP vaccination does not = a distemper vaccination.
For more information on viruses, and to further check out the various virus capsid structures I now refer you to the Viral Zone! It's a really awesome sight so I highly encourage you to check it out!!!