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Arenavirus

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By VISHNU Vexplorehealth

 

Arenavirus

An arenavirus is a bisegmented ambisense RNA virus that is a member of the family Arenaviridae.[1] These viruses infect rodents and occasionally humans. A class of novel, highly divergent arenaviruses, properly known as reptarenaviruses, have also been discovered which infect snakes to produce inclusion body disease. At least eight arenaviruses are known to cause human disease. The diseases derived from arenaviruses range in severity. Aseptic meningitis, a severe human disease that causes inflammation covering the brain and spinal cord, can arise from the lymphocytic choriomeningitis virus. Hemorrhagic fever syndromes, including Lassa fever, are derived from infections such as Guanarito virus, Junin virus, Lassa virus, Lujo virus,[2] Machupo virus, Sabia virus, or Whitewater Arroyo virus.[3] Because of the epidemiological association with rodents, some arenaviruses and bunyaviruses are designated as roboviruses.

Arenaviridae
Viruses-04-02973-g002.webp
(A) Electron micrograph of Lassa virus, bar = 100nm (B) diagram and (C) genome of arenavirus
Virus classificatione
(unranked):Virus
Realm:Riboviria
Kingdom:Orthornavirae
Phylum:Negarnaviricota
Class:Ellioviricetes
Order:Bunyavirales
Family:Arenaviridae
Genera

StructureEdit

Mammarenavirus structure and genome composition.

Viewed in cross-section, arenaviruses contain grainy particles that are ribosomes acquired from their host cells. It is from this characteristic that they acquired the name arena, from the Latin root meaning sand. The ribosomal structures are not believed to be essential for virus replication. Virus particles, or virions, are pleomorphic (variable in shape) but are often spherical, with a diameter of 60–300 nm, and are covered with surface glycoprotein spikes.[4]

The virus contains a beaded nucleocapsid with two single-stranded RNA segments. The nucleocapsid consists of a core of nucleic acid enclosed in a protein coat. Although they are categorized as negative-sense viruses,[5] arenaviruses are ambisense. While sections of their genome encode genes in the negative sense (reverse polarity), other sections encode genes in the opposite (forward/positive sense) direction. This complex gene expression structure is theorized to be a primitive regulatory system, allowing the virus to control what proteins are synthesized at what point in the life cycle. The life cycle of the arenavirus is restricted to the cell cytoplasm.


GenomeEdit

Genomes of Arenaviridae

Arenaviruses have a segmented RNA genome that consists of two single-stranded ambisense RNAs.[6] As with all negative-sense RNA viruses, the genomic RNA alone is not infectious and the viral replication machinery is required to initiate infection within a host cell.[7] Genomic sense RNA packaged into the arenavirus virion is designated negative-sense RNA, and must first be copied into a positive-sense mRNA in order to produce viral protein.[8] The two RNA segments are denoted Small (S) and Large (L),[6][9] and code for four viral proteins in a unique ambisense coding strategy.[10][11] Each RNA segment codes for two viral proteins in opposite orientation such that the negative-sense RNA genome serves as the template for transcription of a single mRNA and the positive-sense copy of the RNA genome templates a second mRNA.[8] The separate coding sequences of the two viral proteins are divided by an intergenic region RNA sequence that is predicted to fold into a stable hairpin structure.[12]

The extreme termini of each RNA segment contains a 19 nucleotide highly conserved sequence that is critical for recruitment of the viral replication machinery and initiation of viral mRNA transcription and genomic replication.[13][14][15][16][17] The conserved 5' and 3' RNA termini sequences are complementary and allows each RNA segment to adopt a double-stranded RNA panhandle structure [18] that maintains the termini in close proximity and results in a circular appearance to purified arenavirus genomic templates visualized by electron microscopy.[19][20] The double-stranded RNA panhandle structure is critical for efficient viral RNA synthesis,[16][21] but potential interterminal double-stranded RNA interactions must be transiently relieved in order to recruit the viral polymerase.[17]

The S-segment RNA is approximately 3.5 kb, and encodes the viral nucleocapsid protein (NP) and glycoprotein (GPC).[22] The L-segment RNA is approximately 7.2 kb, and encodes the viral RNA-dependent RNA-polymerase (L) and a small RING-domain containing protein (Z).[23][24][25]

The Z protein forms homo oligomers and a structural component of the virions.[26] The formation of these oligomers is an essential step for particle assembly and budding. Binding between Z and the viral envelope glycoprotein complex is required for virion infectivity. Z also interacts with the L and NP proteins. Polymerase activity appears to be modulated by the association between the L and Z proteins. Interaction between the Z and NP proteins is critical for genome packaging.

MicrobiologyEdit

Arenavirus replication cycle.

The glycoprotein (GP) is synthesised as a precursor molecule.[27] It is cleaved into three parts - GP1, GP2 and a stable signal peptide (SSP). These reactions are catalysed by cellular signal peptidases and the cellular enzyme Subtilisin Kexin Isozyme-1 (SKI-1)/Site-1 Protease (S1P). These processes are essential for fusion competence and incorporation of mature GP into nascent budding virion particles.

TaxonomyEdit

Within the family Arenaviridae, arenaviruses were formerly all placed in the genus Arenavirus, but in 2014 were divided into the genera Mammarenavirus for those with mammalian hosts and Reptarenavirus for those infecting snakes.[28][29] Reptarenaviruses and mammarenavirus are separated by an impenetrable species barrier. Infected rodents cannot pass disease onto snakes, and IBD in captive snakes is not transmissible to humans.

A third genus, Hartmanivirus (not to be confused with genus Haartmanvirus of vibrio phages in family Demerecviridae, order Caudovirales), has also been established,[30] including other species that infect snakes. The organisation of the genome of this genus is typical of arenaviruses but their glycoproteins resemble those of filoviruses. Species in this genus lack the matrix protein.

A fourth genus, Antennavirus has also been established[31] to accommodate two arenaviruses found in striated frogfish (Antennarius striatus).[32]

Mammarenaviruses can be divided into two serogroups, which differ genetically and by geographical distribution:[33] When the virus is classified "Old World" this means it was found in the Eastern Hemisphere in places such as Europe, Asia, and Africa. When it is found in the Western Hemisphere, in places such as Argentina, Bolivia, Venezuela, Brazil, and the United States, it is classified "New World". Lymphocytic choriomeningitis (LCM) virus is the only arenavirus to exist in both areas but is classified as an Old World virus. Old and New World area viruses appear to have diverged ~45,000 years ago.[34] The Old World Mammarenaviruses originated ∼23.1-1.88 thousand years ago, most likely in Southern Africa while the New World Mammarenaviruses evolved in the Latin America-Caribbean region ∼41.4-3.3 thousand years ago.

MammarenavirusEdit

Old World complexEdit

Arenavirus taxonomy and location

New World complexEdit

ReptarenavirusEdit

HartmanivirusEdit

AntennavirusEdit

  • Hairy antennavirus
  • Striated antennavirus (type species)

  • EvolutionEdit

    The evolution of the Mammarenavirus genus has been studied.[34] The New World and Old World species diverged less than 45,000 years ago. The New World species evolved between 41,400 and 3,300 years ago in the Latin America-Caribbean region. The Old World species evolved between 23,100 and 1,880 years ago, most likely in southern Africa.

  • ReservoirsEdit

    Some arenaviruses are zoonotic pathogens and are generally associated with rodent—transmitted disease in humans. Each virus usually is associated with a particular rodent host species in which it is maintained. Arenaviruses persist in nature by infecting rodents first and then transmitted into humans. Humans can be infected through mucosal exposure to aerosols, or by direct contact of abraded skin with the infectious material, derived from infected rodents.[4] Aerosols are fine mists or sprays of rodent dried excreta, especially urine that is dropped in the environment. Most of the Arenaviruses caught by humans are within their own homes when these rodents seek shelter. The virus can be caught in factories, from food that has been contaminated, or within agricultural work areas. Humans' risk of contracting the Arenavirus infection is related to age, race, or sex within the degree of contact with the dried rodent excreta.

  • EpidemiologyEdit

    HostsEdit

    Arenavirus diseases and hosts
    VirusDiseaseHostDistribution
    Dandenong [35]Dandenong hemorrhagic feverUnknownold world ( Australian cases from Serbia )
    Lymphocytic choriomeningitis virusLymphocytic choriomeningitisHouse mouse (Mus musculus)Worldwide
    Lassa virusLassa feverNatal Multimammate Mouse (Mastomys natalensis)West Africa
    Junin virusArgentine hemorrhagic feverDrylands Vesper Mouse (Calomys musculinus)Argentina
    Machupo virusBolivian hemorrhagic feverLarge Vesper Mouse (Calomys callosus)Bolivia
    Guanarito virusVenezuelan hemorrhagic feverShort-tailed Cane Mouse (Zygodontomys brevicauda)Venezuela
    Sabiá virusBrazilian hemorrhagic feverUnknownBrazil
    Tacaribe virusBat (Artibeus)Trinidad
    Flexal virusInfluenza-like illnessRice rat (Oryzomys)Brazil
    Whitewater Arroyo virusHemorrhagic feverWoodrat (Neotoma)Southwestern United States

    Clinical diseasesEdit

    Comparison of disease phenotypes of OW and NW arenaviruses
    1. Lymphocytic choriomeningitis (LCM) viruses cause influenza-like febrile illness, but occasionally they may cause meningitis, characteristically accompanied by large numbers of lymphocytes in the cerebrospinal fluid (as the name LCM suggests).
    2. Lassa virus causes Lassa fever. Lassa fever is endemic in west Africa. The virus was first isolated from Americans stationed in the village of Lassa, Nigeria. The virus can be transmitted person-to-person.
      • Subclinical diseases: Serological studies suggest that inapparent infections particularly among members of hunting tribes are common.
      • Clinical infections: Lassa fever is characterised by high fever, severe myalgia, coagulopathy, haemorrhagic skin rash, and occasional visceral haemorrhage as well as necrosis of liver and spleen.
    3. Other Arenaviruses like Junin virus, Machupo virus cause haemorrhagic fevers.

    All of these diseases pose a great threat to public health in the regions where it is taking place. For example, when the Old World Lassa virus turns into Lassa fever, this usually results in a significant amount of mortality. Similarly the New World Junin virus causes Argentine hemorrhagic fever. This fever is a severe illness with hemorrhagic and neurological manifestations and a case fatality of fifteen to thirty percent.[4] The way this virus spreads is through increased traveling to and from endemic regions. This traveling has led to the importation of Lassa fever into non-endemic metropolitan areas all over the world.

    Recent outbreaksEdit

    A new species of arenavirus named the Lujo virus has been linked to five patients who exhibited symptoms of viral hemorrhagic fever in South Africa.[36] The disease originated near Lusaka, Zambia and spread to Johannesburg, South Africa, after the first patient was transported to a hospital there. The results of genetic sequencing tests conducted by epidemiologists at Columbia University in New York City, USA, and at the Special Pathogens Branch of the Centers for Disease Control in Atlanta, USA, provided evidence that the causative agent of the disease is a virus from the family Arenaviridae, which ultimately resulted in the deaths of four out of the five infected in Zambia and South Africa during the outbreak which began in September 2008.

    Arenavirus has also pinpointed as the cause of death of three donor organ recipients in Australia who contracted the virus after receiving kidney and a liver donations from a single infected organ donor in late 2006. All three died in the first week of 2007.[37] [38]

    WHO and its Global Outbreak Alert and Response Network (GOARN) partners continue to support the Ministries of Health of the two countries in various facets of the outbreak investigation, including laboratory diagnosis, investigations, active case finding and follow-up of contacts.[39]

  • TreatmentsEdit

    Very few treatment methods are available. The current lack of a licensed vaccine and limited therapeutic options for the arenavirus make it arguably among the most neglected virus groups. The only licensed drug for the treatment of human arenavirus infection is the nucleoside analogue ribavirin.[40] Ribavirin reduces morbidity and mortality in humans infected with certain arenaviruses, such as LASV and JUNV infections, if it is taken in the early stages of the disease. Ribavirin displays mixed success in treating severe arenaviral disease and is associated with significant toxicities.[41]

    Experimental approachesEdit

    Effective antiviral drugs need to be produced at a low cost, taken orally, and able to withstand tropical climates due to the regions where these infections are occurring. For this reason high throughput screening (HTS) of small molecular libraries could be the answer to finding a better remedy. HTS collects libraries of small synthetic molecules that can be used to identify protein promoting "agonist" molecules or protein inhibiting "antagonist" interactions.[40] With HTS sustainable antiviral drugs can be discovered against possible new human pathogenic viruses.

    Immunotherapy is another potential approach. Monoclonal antibodies against Junin virus have been tested in animal models. An immunotherapeutic agent active against all tested mammarenaviruses that use the transferrin receptor 1 as their receptor was under investigation in 2020.[42]

ReferencesEdit

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Nutrition Facts

By VISHNU Vexplorehealth
  What Is Dragon Fruit and Does It Have Health Benefits Dragon fruit is a tropical fruit that has become increasingly popular in recent years. Though people primarily enjoy it for its unique look and taste, evidence suggests it may provide health benefits as well. This article takes a look at dragon fruit, including its nutrition, benefits, and how to eat it. Share on Pintere What Is Dragon Fruit? Dragon fruit grows on the  Hylocereus  cactus, also known as the Honolulu queen, whose flowers only open at night. The plant is native to southern Mexico and Central America. Today, it is grown all over the world. It goes by many names, including pitaya, pitahaya, and strawberry pear. The two most common types have bright red skin with green scales that resemble a dragon — hence the name. The most widely available variety has white pulp with black seeds, though a less common type with red pulp and black seeds exists as well. Another variety — referred to as yellow dragon fruit — has yellow sk
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Brain Basics: Understanding Sleep

By VISHNU Vexplorehealth
Health Brain Basics: Understanding Sleep Anatomy of Sleep Sleep Stages Sleep mechanisms How Much Sleep Do You Need? Dreaming The Role of Genes and Neurotransmitters Tracking Sleep Through Smart Technology Tips for Getting a Good Night's Sleep Hope Through Research Where can I get more information? Introduction Sleep is an important part of your daily routine—you spend about one-third of your time doing it.  Quality sleep – and getting enough of it at the right times -- is as essential to survival as food and water.  Without sleep you can’t form or maintain the pathways in your brain that let you learn and create new memories, and it’s harder to concentrate and respond quickly. Sleep is important to a number of brain functions, including how nerve cells (neurons) communicate with each other.  In fact, your brain and body stay remarkably active while you sleep.  Recent findings suggest that sleep plays a housekeeping role that removes toxins in your brain tha
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Fungal diseases

By VISHNU Vexplorehealth
Health Fungal diseases  About fungal diseases . Fungi are everywhere. Sometimes, they are too small to see with the naked eye. Fungi live: Outdoors, for example, in soil and on plants Indoors, on surfaces and in the air On people’s skin and inside the body There are millions of fungal species, but only a few hundred of them can make people sick. Molds, yeasts, and mushrooms are all types of fungi. Fungi can cause many different types of illnesses, including: Asthma or allergies.  Learn more about mold and how it can affect your health. Rashes or infections on the skin and nails Lung infections (pneumonia), with symptoms similar to the flu or tuberculosis Bloodstream infections Meningitis   Most common fungal diseases Fungal nail infections Common infections of the fingernails or toenails. Vaginal candidiasis Caused by the yeast  Candida , also called a “vaginal yeast infection.” Ringworm A common fungal skin infection that often looks like a circular rash. Candida  infections of the mo
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Brain’s waste removal system

By VISHNU Vexplorehealth
Health Brain’s waste removal system may offer path to better outcomes in Alzheimer’s therapy NIH-funded study in mice suggests lymphatic boost could help reduce amyloid buildup. Study of mouse brain shows the meningeal lymphatics system (purple and pink) could help reduce amyloid. Sandro Da Mesquita, Ph.D. Enhancing the brain’s lymphatic system when administering immunotherapies may lead to better clinical outcomes for Alzheimer’s disease patients, according to a new study in mice. Results published April 28 in Nature suggest that treatments such as the immunotherapies BAN2401 or aducanumab might be more effective when the brain’s lymphatic system can better drain the amyloid-beta protein that accumulates in the brains of those living with Alzheimer’s. Major funding for the research was provided by the National Institute on Aging (NIA), part of the National Institutes of Health, and all study data is now freely available to the broader scientific community. “A broad ra
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Health info / news/

By VISHNU Vexplorehealth
Vexplorehealth Health Information News Helpful Tips for Managing Chronic Kidney Disease Chronic kidney disease (CKD) is a serious condition affecting 37 million U.S. adults and is often overlooked until symptoms appear. As we continue to observe  National Kidney Month  this March, learn how adopting a healthy lifestyle can help manage and slow the progression of CKD and its complications. Watch this video for tips to help people with CKD take charge of their kidney health.
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Spinal muscular atrophy

By VISHNU Vexplorehealth
 Spinal muscular atrophy Two-Month-Old Baby Battling Rare Disease To Receive World’s Most Expensive Injection Suffering from genetic spinal muscular atrophy, the baby is undergoing gene theray and will require an injection that costs Rs 16 Crores An eight-week-old baby in Britain will receive an injection that costs about Rs. 16 Crores, reports claimed. Suffering from genetic spinal muscular atrophy, Edward will have to be administered one type of gene therapy—Zolgensma to fight the rare disease. Since Britain imports the doses from the US and Europe, the injection costs a whooping a 1.7 million pounds. A disease unique to children, genetic spinal muscular atrophy (SMA), occurs due to lack of the SMN-1 gene. Symptoms of the disease include weakening of chest muscles which eventually leads to a difficulty in breathing. Interestingly, until 2017 there was no cure for the disease. Spinal Muscular Atrophy Download our Spinal Muscular Atrophy Fact Sheet Learn about MDA’s COVID-19 response W
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Women crying: is it emotionally beneficial?

By VISHNU Vexplorehealth
 Do you know women will cry 4,680 times over in their adult life which is more than twice as much as men? Crying is a common human activity, and it can be triggered by many different emotions. But what do you think women crying is emotionally beneficial? According to the psychologist women are stereotypically associated with crying. It has benefit for both your mind and body. Check out all the health benefits of crying. Why do women crying have health benefits? It is said the women crying have benefit for both body and their mind. These crying benefits begin at birth with a baby’s first cry. Keep reading and learn more about the benefits of women crying. 1. Detoxifies body There are three different types of tears: Reflex tears Continuous tears Emotion tears Reflex tears are 98% water which clear debris like smoke and dust from your eyes. Emotional tears also contain stress hormones and toxins, while continuous tears also contain 98 per cent of water. When you cry, you are effectively d
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