Transmissible gastroenteritis virus

# Overview
Transmissible Gastroenteritis Coronavirus (TGEV) is a species of animal virus belonging to the family Coronaviridae. TGEV are enveloped viruses with a positive-sense single-stranded RNA genome and a helical symmetry. The genomic size of coronaviruses ranges from approximately 28.6 kilobases.
Proteins that contribute to the overall structure of TGEV includes the spike (S), envelope (E), membrane (M) and nucleocapsid (N). TGEV is a group I coronavirus. Other group 1 coronaviruses include Canine coronavirus, Feline coronavirus, Human coronavirus 229E, and Porcine epidemic diarrhea virus.

# TGEV Biology
TGEV belongs to the coronavirus family. It is an enveloped virus with a positive single stranded RNA genome. TGEV has three major structural proteins, which are phosphoprotein (N), integral membrane protein (E1), and large glycoprotein (E2). The N protein encapsulates the genomic RNA, and the S protein forms viral projections.
The 3' segment of about 8000 nucleotides encodes subgenomic RNAs. The remaining part of the genome encodes viral replicase. The three largest gene sequence from 5' to 3' is in the order of E2 to E1 to N. There are about seven other open reading frames that are not structurally related. There are very little overlaps among the genes, and is densely packed. A negative strand is synthesized to serve as a template for transcribing RNAs of one genome size and several subgenome sized RNAs.
The E2 protein forms a petal-shaped 20 nm long projection from the virus's surface. The E2 protein is thought to be involved in pathogenesis by helping the virus enter the host cytoplasm. The E2 protein initially has 1447residues, and then a short hydrophobic sequence is cleaved. After glycosylation of the protein in the golgi, the protein is then incorporated into the new virus. There are several functional domains within the E2 protein. A 20 residue hydrophobic segment at the C-terminus anchors the protein in the lipid membrane. The rest of the protein is divided into two parts, a hydrophilic stretch that is inside the virus and a cysteine rich stretch that are possibly fatty acylation sites. The E1 protein is mostly embedded in the lipid envelop and hence plays an essential role in virus architecture. The E1 protein is postulated to interact with the lymphocyte membrane, which leads to the induction of IFN-coding genes.

# TGEV Morphology
The morphology of TGEV was mostly determined by electron microscopy techniques. The morphology is similar to myxovirus and oncogenic virus in that they have surface projections and an envelop. The viruses are mainly circular in shape with a diameter ranging from 100 to 150 um including the surface projections. The projections were mainly petal-shaped attached by a very narrow stalk. The projections seemed to be very easily detached from the virus and were only found on select areas.

# TGEV pathology
TGEV infects both pigs and humans. However, in young pigs, the mortality rate is close to 100%. The pathology of TGEV is similar to that of other coronaviruses. Coronaviruses enter the host by first attaching to the host cell using the spike glycoprotein. The S protein interacts with the procine aminopeptidase N (pAPN), a cellular receptor, to aide in its entry. The same cell receptor is also a point of contact for Human Coronaviruses. A domain in the S spike protein is recognized by pAPN, and transfection of pAPN occurs to nonpermissive cells and infects them with TGEV. Once the virus infects the host, it multiplies in the cell lining of the small intestine resulting in the loss of absorptive cells that in turn leads to shortening of villi. The infected swine then has reduced capability for digesting food and die from dehydration.

# Engineering TGEV coronavirus
The Transmissible Gastroenteritis Virus has been engineered as an expression vector. The vector was constructed by replacing the nonessential 3a and 3b ORF, which is driven by the transcription-regulating sequences (TRS) with green fluorescent protein. The resulting construct was still enteropathogenic, but with reduced growth. The infection of cells with this altered virus elicits a specific lactogenic immune response against the heterologous protein. The application of this vector is in the development of a vaccine or even gene therapy. The motivation for engineering the TGEV genome is that coronaviruses have large genomes, so they have room for insertion of foreign genes. Coronaviruses also infect the respiratory track, and they can be used to target antigens to that area and generate some immune response.