Virus biology There are several strains of<unk>  virus, among which the most widely used are<unk> V Armstrong and<unk> V Clone 13. Armstrong is the original virus strain which was isolated from the brain by Charles Armstrong in 1934. It triggers a vigorous cytotoxic T lymphocytes(CTL) response and thus, it is cleared rapidly by the host. This is referred to as acute (Armstrong)<unk> V infection. On the other hand, Clone 13 is a variant of the Armstrong viral strain, isolated from the spleen and is consequently tropic for visceral organs. It was first isolated from mice which sustained a persistent<unk> V infection from birth. This variant potentiates a less vigorous CTL response in the immune system, and thus can ultimately persist in the host organism indefinitely. The latter is referred to as chronic (Clone 13)<unk> V infection.<unk> V is a spherical enveloped virus with a diameter between 60 and 300 nm. The helical nucleocapsid contains an RNA genome consisting of two negative single-stranded RNA segments. The negative RNA strand, complementary to the necessary mRNA strand, indicates that it must first be transcribed into a positive mRNA strand before it can be translated into the required proteins. The L strand is ambisense RNA, encoding multiple proteins in opposite directions, separated by an intergenic region. It is approximately 7.2 kb in size and encodes a high-molecular-mass protein (L; 200 kDa) and an 11 kDa small polypeptide Z with unknown function and a ring finger motif. The viral RNA-dependent RNA polymerase is encoded by the L protein which contains conserved characteristic motifs throughout all the RNA-dependent, RNA-polymerases. The S strand is ambisense and approximately 3.4 kb in size. It encodes the two main structural proteins: nucleo-protein (NP) (63 kDa) and glycoprotein precursor complex (GPC) (75kDa). The latter undergoes posttranslational cleavage at two separate steps: first in the endoplasmic reticulum, where following translation on the membrane, the stable signal peptide region is cleaved by signal peptidase (SPase); notably, this signal peptide is retained, in contrast to other viruses. The second cleavage occurs at the Golgi apparatus, where GP1-GP2, having been trafficked to the Golgi, is cleaved into separate mature viral glycoproteins, GP1 and GP2 (with cleavage mediated by SK1-/PS1 or MTBPS1). The spikes present on the virion envelope are dictated by tetramer formation of GP-1 and GP-2. When<unk> V attacks a cell, the process of replication starts by attachment of the virus to host receptors through its surface glycoproteins. It is then endocytosed into a vesicle inside the host cell and creates a fusion of the virus and vesicle membranes. The ribonucleocapsid is then released in the cytoplasm. The RNA-dependent, RNA-polymerase brought along with the virus initially binds to a promoter on the L and S segments and begins transcription from negative-stranded to a positive-stranded mRNA. The formation of a strong hairpin sequence at the end of each gene terminates transcription. The mRNA strands are capped by the RNA-dependent, RNA-polymerase in the cytoplasm and are then subsequently translated into the four proteins essential for<unk> V assembly. The ribonucleocapsid interacts with the Z matrix protein and buds on the cell membrane, releasing the virion out from the infected cell. The first arenavirus,<unk>  mammarenavirus <unk> V), was isolated in 1933 by Charles Armstrong during a study of an epidemic in St. Louis. Although not the cause of the outbreak,<unk> V was found to be a cause of nonbacterial or aseptic meningitis. In 1996, Peter Doherty and Rolf Zinkernagel shared the Nobel Prize in Medicine and Physiology, for their work with<unk> V which led to a fundamental understanding of the adaptive immune response, MHC restriction. In the 1970s, studies concerning the importance of MHC locus were done exclusively in transplantation and tumor rejection. Taking this into consideration, Doherty and Zinkernagel were working on the response of mice to virus infections. They observed that T-cell receptors must recognise a complex of foreign antigen and an MHC antigen in order to destroy infected cells. Their key experiment involved harvesting of splenocytes containing<unk> V-specific cytotoxic T lymphocytes(CTL) from an infected mouse strain A. These were then mixed in vitro with virus infected fibroblasts or macrophages from two different mouse strains, A and B. By the method of Cr-release cytotoxicity assay, thereby tagging the CTL with chromium-51 (Cr-51), the CTL destruction of infected cells was quantified by release of Cr-51. The results showed that CTL killed only the infected cells from strain A, and they did not lyse uninfected cells or infected cells from strain B. They concluded that these virus specific CTLs only lyse cells carrying the same molecules of the major histocompatibility site (MHC) as the CTLs themselves. Thus, the virus-specific CTLs are "MHC-restricted". This discovery lead to a greater understanding of an important aspect of the immune system. Spread<unk> V is naturally spread by the common house mouse, Mus musculus. Once infected, these mice can become chronically infected by maintaining virus in their blood or persistently shedding virus in their urine. Chronically infected female mice usually transmit infection to their offspring (vertical transmission), which in turn become chronically infected. Other modes of mouse-to-mouse transmission include nasal secretions, milk from infected dams, bites, and during social grooming within mouse communities. Airborne transmission also occurs. The virus seems to be relatively resistant to drying and therefore humans can become infected by inhaling infectious aerosolized particles of rodent urine, feces, or saliva, by ingesting food contaminated with virus, by contamination of mucous membranes with infected body fluids, or by directly exposing cuts or other open wounds to virus-infected blood. The only documented cases of transmission from animals have occurred between humans and mice or hamsters. Cases of<unk>  have been reported in North and South America, Europe, Australia, and Japan, particularly during the 1900s. However, infection may occur wherever an infected rodent host population exists.<unk> V occurs worldwide and its natural host, the rodent, has become established on all continents, except Antarctica. Seroprevalence is approximately 5% (0.7–4.7%) of the US population. It tends to be more common among lower socio-economic groupings, probably reflecting more frequent and direct contacts with mice. However, obtaining an accurate sense of prevalence by geographic region is difficult due to underreporting. Congenital infection<unk>  is a particular concern in obstetrics, as vertical transmission is known to occur. For immunocompetent mothers, there is no significant threat, but the virus has damaging effects upon the fetus. If infection occurs during the first trimester,<unk> V results in an increased risk of spontaneous abortion. Later congenital infection may lead to malformations such as intracranial calcifications, hydrocephalus, microcephaly or macrocephaly, intellectual disabilities, and seizures. Other findings include chorioretinal scars, and optic atrophy. Chorioretinitis, which is followed by chorioretinal scarring, is the most common ocular lesion. Mortality among infants is approximately 30%. Among the survivors, two-thirds have lasting neurologic abnormalities. Other ocular defects including optic atrophy, microphthalmia, vitreitis, leukokoria and cataracts can also be seen. Most of the infants in one case series were of normal birth weight, although 30% were underweight. Aspiration pneumonia can be a fatal complication. Infants who survive may have severe neurological defects including epilepsy, impaired coordination, visual loss or blindness, spastic diplegia or quadriparesis/quadriplegia, delayed development and intellectual disability. Less severe cases with isolated cerebellar hypoplasia and symptoms of ataxia and jitteriness have been reported occasionally. There have also been rare cases with evidence of chorioretinitis but without neurological signs. Systemic signs seem to be rare, but hepatosplenomegaly, thrombocytopenia and hyperbilirubinemia have been documented in a few cases, and skin blisters were reported in one infant. If a woman has come into contact with a rodent during pregnancy and<unk>  symptoms are manifested, a blood test is available to determine previous or current infection. A history of infection does not pose a risk for future pregnancies. Organ donation Patients infected in solid organ transplants have developed a severe fatal illness, starting within weeks of the transplant. In all reported cases, the initial symptoms included fever, lethargy, anorexia and leukopenia, and quickly progressed to multisystem organ failure, hepatic insufficiency or severe hepatitis, dysfunction of the transplanted organ, coagulopathy, hypoxia, multiple bacteremias and shock. Localized rash and diarrhea were also seen in some patients. Nearly all cases have been fatal. In May 2005, four solid-organ transplant recipients contracted an illness that was later diagnosed as<unk> . All received organs from a common donor, and within a month of transplantation, three of the four recipients had died as a result of the viral infection. Epidemiologic investigation traced the source to a pet hamster that the organ donor had recently purchased from a Rhode Island pet store. Similar cases occurred in Massachusetts in 2008, and Australia in 2013. There is not a<unk> V infection test that is approved by the Food and Drug Administration for organ donor screening. The Morbidity and Mortality Weekly Report advises health-care providers to "consider<unk> V infection in patients with aseptic meningitis and encephalitis and in organ transplant recipients with unexplained fever, hepatitis, or multisystem organ failure."
Lymphocytic choriomeningitis
Meningeal syphilis
Granulomatous meningoencephalitis
Progressive rubella panencephalitis
Drug-induced aseptic meningitis
Oropouche fever
Meningitis
Amoebic brain abscess