Junin virus
1. Introduction
Classification of Junin Virus
- Superkingdom
- Viruses
- Domain
- Riboviria
- Kingdom
- Orthonavirae
- Phylum
- Negarnviricota
- Subphylum
- Polyploviricotina
- Class
- Ellioviricetes
- Order
- Bunyavirales
- Genus
- Arenaviridae
- Species
- Mammarenavirus
- Common Names
- Argentine Mammarenavirus, Junin Virus, Junin Arenavirus, JUNV
2. Description and significance
Describe the appearance, habitat, etc. of the organism, and why you think it is important.
- Include as many headings as are relevant to your microbe. Consider using the headings below, as they will allow readers to quickly locate specific information of major interest*
3. Genome structure
Junin Virus has a negative-sense double-stranded RNA genome that is made up of two segments: the large (L), which is 7.3 kbp, and the small (S), which is 3.5 kbp[6]. The two segments are configured in an ambisense orientation, which means the information on each strand is read in the opposite direction from the other[6]. The genome of the Junin Virus codes for four proteins. The L segment encodes a viral RNA polymerase called L polymerase, as well as a small zinc-binding protein called RING finger protein Z[6]. The S segment encodes the glycoprotein precursor (GPC) and the nucleoprotein (NP)[6]. The NP protein is the first protein that is translated. After translation of GPC, the protein is cleaved into two new glycoproteins: GP1 and GP2. GP1 is inserted in the peripheral membrane of the viral envelope, and GP2 becomes part of the integral membrane[7]. These proteins in the bilayer are involved in recognition and the entry of the virus into target cells. The cleaving of GPC also yields a signal stable peptide (SSP), which ensures that GPC responds properly to acidic conditions[6].
4. Cell structure
Junin Virus is coated in a viral envelope consisting of a phospholipid bilayer and glycoproteins. Its shape can be pleomorphic (meaning shapes can vary) or spherical[2]. It has a diameter of 110-130 nm and has several glycoprotein spikes embedded in the lipid bilayer that are each 8-10 nm long[2]. These spikes are made up of the glycoproteins GP1 and GP2, which are produced by cleaving the glycoprotein precursor (GPC), a protein that is encoded in the viral genome[2]. The glycoprotein spike is club-shaped, with the head of the club consisting of a GP1 tetramer and the stem consisting of a GP2 tetramer[2]. The nucleoprotein (NP) is another protein encoded in the viral genome, and it associates with the viral RNA to form nucleocapsid structures in the cytoplasm of the infected cell[2]. The lipid membrane of the virus has its origin in the host cell membrane, and packaged inside are ribosomes also derived from the host cell[2]. It is currently unknown if the ribosomes serve any purpose[2].
5. Metabolic processes
Describe important sources of energy, electrons, and carbon (i.e. trophy) for the organism/organisms you are focusing on, as well as important molecules it/they synthesize(s).
6. Ecology
The Junin Virus, also known as “Argentine Mammarenavirus” is mainly found in central Argentina where the majority of farming occurs[2]. This is because it is a virus contracted from Calomys musculinus mice native to this region[2]. As a result of the frequent contact with these rodents, mostly farmers are impacted by this virus and it first arose through a jump from mice to humans in the 1950s[2]. It also can infect other small rodent hosts like rabbits and guinea pigs[2]. These infections are caused by multiple different strains of Junin Virus of multiple different virulences. The most virulent strain was dubbed “Romero”. Originally, when Junin Virus was first discovered, since it led to hemorrhagic fever, the fatality rate was higher(around 16.5%, however once the vaccine was introduced, fatality decreased exponentially[2]. Scientifically the Junin Virus is classified as a biosafety level four pathogen meaning that it is highly virulent and if handled in a lab environment requires extreme precautions. [citation].
Junin virus requires a pH less than 6.1 to enter the host cell membrane via endocytosis [9] but is inactivated at pH below 5.5 or above 8.5 [21,22]. The virus is also sensitive to heat and inactivated if exposed to a temperature of 56°C for at least 30 minutes. Junin virus is also inactivated by gamma irradiation and UV radiation [21,22].
7. Pathology
How does this organism cause disease? Human, animal, plant hosts? Virulence factors, as well as patient symptoms.
8. Current Research
Junin Virus research focuses on viral replication machinery, host-virus interactions, treatment, and vaccination. In a human host, the Junin virus has been shown to use its Z protein to hijack human ribosomal proteins, Ras proteins, endosome sorting proteins, and ATP synthesis proteins[12].Another discovery relating to how the Junin Virus interacts with and hijacks human proteins focuses on the virus’ use of the Type 1 Interferon in humans to enter cells [13]. Once inside the cell, this interaction is one of the ways the Junin Virus can cause Argentine Hemorrhagic Fever (AHF)[14]. It was found that when mice were infected with the Junin virus, the mice that had a higher concentration of Type 1 Interferon had more severe AHF symptoms than mice that had a lower concentration[14]. Research into these areas gives the scientific community a more thorough understanding of how JUNV impacts its host and can be used to make more informed decisions on treatment and vaccination against the Junin Virus. Research and discoveries regarding Junin Virus antibodies are also being explored. Experiments being conducted suggest that a glycoprotein present in the Junin Virus vaccine may also be effective in protecting against the Machupo virus, another New World arenavirus[15]. In particular in mice, a recombinant glycoprotein from the Junin Virus strain protected them from the Machupo virus, showing significant reductions in death and infection [16], [17]. These findings allow the possibility of the application of vaccines against more than one virus.
Another emerging area of research is the effect of specific inhibitors on different metabolic pathways of the Junin virus. Two inhibitors, brefeldin A (BFA) and carbonyl cyanide m-chlorophenylhydrazone (CCCP), have been shown to affect the maturation process of the virus by disrupting the virus’s intracellular exocytic pathway [11]. CCCP alters the distribution of glycoproteins in the cell by blocking its transport from the endoplasmic reticulum to the plasma membrane. The disruption in this exocytic pathway leads to an accumulation of JV glycoproteins at the endoplasmic reticulum surface [11]. BFA disrupts the maturation of glycoproteins in the Golgi apparatus GP38 is a glycoprotein responsible for virus attachment to the host cell [11]. Disruption in the transport and maturation of this GP is required for both the maturation and entry of JV into the cell [11], [16]. The combined effect of CCCP and BFA restrict the formation and multiplication of the Junin Virus. Further research in this area is being conducted to gain a better understanding of the complex physiological pathways of the JV and investigate the scope of such inhibitors in the treatment of Argentine Hemorrhagic Fever.
Novel vaccine research has found a potential new way to vaccinate against the Junin Virus that is safer than the current Candid 1 vaccine. The Candid 1 vaccine uses a live-attenuated version of the Junin Virus has, in some cases, been shown to revert to its more virulent form[19]. In light of this potentiality for reversal, the FDA will not approve the Candid 1 vaccine for use in the U.S. A new attenuated version of the Junin virus was developed that was unable to be reverted to its more virulent form, making it a safer option to the Candid 1 vaccine[19]. This new vaccine candidate, when tested in guinea pigs, was able to protect against the Junin Virus while simultaneously not reverting to its original virulent form[19]. Continuing research into safer vaccines for the Junin Virus provides a safer landscape for the citizens of Argentina to live in and contributes to the larger index of information on how vaccines can be made for other viruses.
9. References
It is required that you add at least five primary research articles (in same format as the sample reference below) that corresponds to the info that you added to this page. [Sample reference] Faller, A., and Schleifer, K. "Modified Oxidase and Benzidine Tests for Separation of Staphylococci from Micrococci". Journal of Clinical Microbiology. 1981. Volume 13. p. 1031-1035.
