# Remedy/Viruses

This negative stained transmission electron micrograph (TEM) depicts a number of filamentous Marburg virions, which had been cultured on Vero cell cultures, and purified on sucrose, rate-zonal gradients. Note the virus’s morphologic appearance with its characteristic “Shepherd’s Crook” shape; Magnified approximately 100,000x. Marburg hemorrhagic fever is a rare, severe type of hemorrhagic fever which affects both humans and non-human primates. Caused by a genetically unique zoonotic (that is, animal-borne) RNA virus of the filovirus family, its recognition led to the creation of this virus family. The four species of Ebola virus are the only other known members of the filovirus family. Marburg virus was first recognized in 1967, when outbreaks of hemorrhagic fever occurred simultaneously in laboratories in Marburg and Frankfurt, Germany and in Belgrade, Yugoslavia (now Serbia).
Def. a "submicroscopic, non-cellular structure consisting of a" "core of DNA or RNA surrounded by a protein coat that requires a living [host] cell to reproduce [replicate] [ and] often causes disease in the host organism"; such agents are often classed as nonliving infectious particles and less often as microorganisms" is called a virus.

## Viruses

A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since an 1892 article describing a non-bacterial pathogen infecting tobacco plants and the discovery of the tobacco mosaic virus in 1898, more than 9,000 virus species have been described in detail of the millions of types of viruses in the environment. Viruses are found in almost every ecosystem on Earth and are the most numerous type of biological entity.

## Infectious doses

The infectious dose of norovirus required to produce infection in humans is less than 100 particles.
The variety of host cells that a virus can infect is called its "host range", which can be narrow, meaning a virus is capable of infecting few species, or broad, meaning it is capable of infecting many.

## Bacteriophages

A group of viruses that infect bacteria, now called bacteriophages was discovered. (or commonly 'phages'). Viruses that, when added to bacteria on an agar plate, would produce areas of dead bacteria. He accurately diluted a suspension of these viruses and discovered that the highest dilutions (lowest virus concentrations), rather than killing all the bacteria, formed discrete areas of dead organisms. Counting these areas and multiplying by the dilution factor allowed him to calculate the number of viruses in the original suspension.

## Adenoviridae

Adenoviruses (members of the family Adenoviridae) are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from their initial isolation from human adenoids in 1953.
They have a broad range of vertebrate hosts; in humans, more than 50 distinct adenoviral serotypes have been found to cause a wide range of adenovirus infection (illnesses), from mild respiratory infections in young children (known as the common cold) to life-threatening multi-organ disease in people with an immunodeficiency (weakened immune system).
This family contains the following genera:
* Atadenovirus
* Aviadenovirus
* Ichtadenovirus
* Mastadenovirus (including all human adenoviruses)
* Siadenovirus
* Testadenovirus
In humans, currently there are 88 human adenoviruses (HAdV serotypes) in seven species (Human adenovirus A to G):
* Human adenovirus A: 12, 18, 31
* Human adenovirus B: 3, 7, 11, 14, 16, 21, 34, 35, 50, 55
* Human adenovirus C: 1, 2, 5, 6, 57
* Human adenovirus D: 8, 9, 10, 13, 15, 17, 19, 20, 22, 23, 24, 25, 26, 27, 28, 29, 30, 32, 33, 36, 37, 38, 39, 42, 43, 44, 45, 46, 47, 48, 49, 51, 53, 54, 56, 58, 59, 60, 62, 63, 64, 65, 67, 69, 70, 71, 72, 73, 74, 75
* Human adenovirus E: 4
* Human adenovirus F: 40, 41
* Human adenovirus G: 52
Different types/serotypes are associated with different conditions:
* respiratory disease (mainly species HAdV-B and C)
* conjunctivitis (HAdV-B and D)
* gastroenteritis (HAdV-F types 40, 41, HAdV-G type 52)
* obesity or adipogenesis (HAdV-A type 31, HAdV-C type 5, HAdV-D types 9, 36, 37)
All these types are called Human mastadenovirus A–G by the International Committee on Taxonomy of Viruses (ICTV), because all are members of the genus Mastadenovirus.
The penton bases are associated with protruding fibers that aid in attachment to the host cell via the receptor on its surface.
The structure of the human adenovirus was solved at the atomic level, making it the largest high-resolution model ever, composed of around 1 million amino acid residues and around 150 MDa.
Orthopoxvirus phylogeny :
| nucleocapsid | envelope | genome | By sequence | By gene content | Genus species | Common name |
| icosahedral | nonenveloped | double-stranded DNA genome | Adenovirus virus | between 26 and 48 Kbp. 22 to 40 genes | Mastadenovirus human A | human adenovirus A |
| icosahedral | nonenveloped | double-stranded DNA genome | Adenovirus virus | between 26 and 48 Kbp. 22 to 40 genes | Mastadenovirus human B | human adenovirus B |
| icosahedral | nonenveloped | double-stranded DNA genome | Adenovirus virus | between 26 and 48 Kbp. 22 to 40 genes | Mastadenovirus human C | human adenovirus C |
| icosahedral | nonenveloped | double-stranded DNA genome | Adenovirus virus | between 26 and 48 Kbp. 22 to 40 genes | Mastadenovirus human D | human adenovirus D |
| icosahedral | nonenveloped | double-stranded DNA genome | Adenovirus virus | between 26 and 48 Kbp. 22 to 40 genes | Mastadenovirus human E | human adenovirus E |
| icosahedral | nonenveloped | double-stranded DNA genome | Adenovirus virus | between 26 and 48 Kbp. 22 to 40 genes | Mastadenovirus human F | human adenovirus F |
| icosahedral | nonenveloped | double-stranded DNA genome | Adenovirus virus | between 26 and 48 Kbp. 22 to 40 genes | Mastadenovirus human G | human adenovirus G |

## Asfarviridae

African swine fever virus (ASFV') is a large, double-stranded DNA virus in the Asfarviridae family, the causative agent of African swine fever (ASF), causes a hemorrhagic fever with high mortality rates in domestic pigs; some isolates can cause death of animals as quickly as a week after infection, persistently infects its natural hosts, warthogs, bushpigs, and soft ticks of the genus Ornithodoros, which likely act as a vector, with no disease signs. It does not cause disease in humans. ASFV is endemic to sub-Saharan Africa and exists in the wild through a cycle of infection between ticks and wild pigs, bushpigs, and warthogs. The disease was first described after European settlers brought pigs into areas endemic with ASFV, and as such, is an example of an emerging infectious disease.
ASFV replicates in the cytoplasm of infected cells. It is the only virus with a double-stranded DNA genome known to be transmitted by arthropods.

## Coronaviridae

Coronaviruses constitute the subfamily Orthocoronavirinae, in the family Coronaviridae, order Nidovirales and realm Riboviria. They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses ranges from approximately 26 to 32 kilobases, one of the largest among RNA viruses.
"Coronaviruses possess the largest genomes [26.4 kb (ThCoV HKU12) to 31.7 kb (SW1)] among all known RNA viruses [...] [2,13,16]." They have characteristic club-shaped peplomer (spikes) that project from their surface, which in electron micrographs create an image reminiscent of the solar corona, from which their name derives. "[T]here is also a characteristic "fringe" of projections 200 A long, which are rounded or petal shaped ... This appearance, recalling the solar corona, is shared by mouse hepatitis virus and several viruses recently recovered from man, namely strain B814, 229E and several others."
Coronavirus phylogeny :
| nucleocapsid | envelope | genome | sense | By sequence | By gene content | Genus species | Common name |
| helical symmetry | enveloped | single-stranded RNA | positive | OC43 | | Alphacoronavirus human coronavirus 229E | Human coronavirus 229E |
Genome organisation of SARS-CoV. Nsp3 and full-length SUD with subdomains N, M, and C are highlighted. Mpro, main (or 3CL) protease; ssRBP, single-stranded RNA-binding protein; RdRp, RNA-dependent RNA polymerase; ExoN, exonuclease; NendoU, uridine-specific endoribonuclease; MT, methyltransferase; Spike, spike protein; E, envelope protein; M, membrane (matrix) protein; N, nucleocapsid protein; Ac, acidic domain; X, X-domain; SUD, SARS-unique domain; PL2pro, papain-like protease; TM, transmembrane region; Y, Y-domain.

## Herpesviridae

Human herpesvirus 3 (HHV-3)
Varicella-zoster virus
Human alphaherpesvirus 3 (HHV-3), usually referred to as the varicella-zoster virus (VZV), is one of nine herpesviruses known to infect humans. It causes chickenpox, a disease most commonly affecting children, teens, and young adults, and shingles in adults; shingles is rare in children. VZV infections are species-specific to humans, but can survive in external environments for a few hours.
Many years after the person has recovered from chickenpox, VZV can reactivate to cause neurological conditions.
Even when clinical symptoms of chickenpox have resolved, VZV remains dormant in the nervous system of the infected person (virus latency), in the trigeminal nerve and dorsal root ganglia.
Lesions most commonly occur on the face, throat, the lower back, the chest and shoulders.
In about a third of cases, VZV reactivates later in life, producing a disease known as shingles or herpes zoster.
The individual lifetime risk of developing herpes zoster is thought to be between 20% and 30%, or approximately 1 in 4 people; however, for individuals aged 85 and over, this risk increases to 1 in 2 people.
In a study from Sweden the annual incidence of herpes zoster infection is estimated at a total of 315 cases per 100,000 inhabitants for all ages and 577 cases per 100,000 for people 50 years of age or older.
VZV can also infect the central nervous system, with an article reporting an incidence rate of 1.02 cases per 100,000 inhabitants in Switzerland, and an annual incidence rate of 1.8 cases per 100,000 inhabitants in Sweden.
Serious complications of varicella zoster infection include Mollaret's meningitis, zoster multiplex, and inflammation of arteries in the brain leading to stroke,
Reye’s syndrome mostly affects children and teenagers, using aspirin during infection can increase this risk.
The tegument is in turn covered by a lipid envelope studded with glycoproteins that are displayed on the exterior of the virion, each approximately 8 nm long.
The genome was first sequenced in 1986. It is a linear duplex DNA molecule, a laboratory strain has 124,884 base pairs. The genome has 2 predominant isomers, depending on the orientation of the S segment, P (prototype) and I$_S$ (inverted S) which are present with equal frequency for a total frequency of 90–95%. The L segment can also be inverted resulting in a total of four linear isomers (I$_L$ and I$_{LS}$). This is distinct from HSV's equiprobable distribution, and the discriminatory mechanism is not known. A small percentage of isolated molecules are circular genomes, about which little is known. (It is known that HSV circularizes on infection.) There are at least 70 open reading frames in the genome.
There are at least five clades of this virus. Clades 1 and 3 include European/North American strains; clade 2 are Asian strains, especially from Japan; and clade 5 appears to be based in India. Clade 4 includes some strains from Europe but its geographic origins need further clarification. There are also four genotypes that do not fit into these clades.
Phylogenetic analysis of VZV genomic sequences resolves wild-type strains into 9 genotypes (E1, E2, J, M1, M2, M3, M4, VIII and IX).
Sequence analysis of 342 clinical varicella and zoster specimens from 18 European countries identified the following distribution of VZV genotypes: E1, 221 (65%); E2, 87 (25%); M1, 20 (6%); M2, 3 (1%); M4, 11 (3%). No M3 or J strains were observed. Of 165 clinical varicella and zoster isolates from Australia and New Zealand typed using this approach, 67 of 127 eastern Australian isolates were E1, 30 were E2, 16 were J, 10 were M1, and 4 were M2; 25 of 38 New Zealand isolates were E1, 8 were E2, and 5 were M1.
The mutation rate for synonymous and nonsynonymous mutation rates among the herpesviruses have been estimated at 1 × 10$^{−7}$ and 2.7 × 10$^{−8}$ mutations/site/year, respectively, based on the highly conserved gB gene.

## Matonaviridae

Rubella virus (Rubivirus rubellae) is assigned to the Rubivirus genus.
Rubiviruses is classified as part of the family Matonaviridae distinguishing rubella from measles and scarlet fever.
The genome has 9,762 nucleotides and encodes 2 nonstructural polypeptides (p150 and p90) within its 5′-terminal two-thirds and 3 structural polypeptides (C, E2, and E1) within its 3′-terminal one-third.
There are three sites that are highly conserved in Matonaviruses: a stem-and-loop structure at the 5' end of the genome, a 51-nucleotide conserved sequence near the 5' end of the genome and a 20-nucleotide conserved sequence at the subgenomic RNA start site. Homologous sequences are present in the rubella genome.
The genome encodes several non-coding RNA structures; among them is the rubella virus 3' cis-acting element, which contains multiple stem-loops, one of which has been found to be essential for viral replication.
The genome has the highest G+C content of any currently known single stranded RNA virus (~70%).
While alphavirus virions are spherical and contain an icosahedral nucleocapsid, RuV virions are pleiomorphic and do not contain icosahedral nucleocapsids.
"Phylogenetic analysis of the RNA-dependent RNA polymerase of alphaviruses, rubella virus and other positive-sense RNA viruses shows the two genera within the Togaviridae are not monophyletic. In particular, rubella virus groups more closely with members of the families Benyviridae, Hepeviridae and Alphatetraviridae, along with several unclassified viruses, than it does with members of the family Togaviridae belonging to the genus Alphavirus."
Rubivirus phylogeny :
| nucleocapsid | envelope | genome | sense | By sequence | By gene content | Genus species | Common name |
| icosahedral | enveloped | single-stranded RNA | positive | three sites | 9,762 nucleotides | Rubivirus rubellae | Rubella virus (RuV) |

## Orthomyxoviridae

"Influenza A and B viruses. (A) Schematic of the eight viral RNA (vRNA) gene segments that comprise the influenza A and B genomes. The 5′ and 3′ untranslated regions (UTRs), which contain the viral promoters, are represented with a line, and the box corresponds to the coding region within each vRNA. (B) Diagram of the viral mRNAs that are transcribed from the IAV (left) and IBV (right) vRNA templates. Boxes indicate the viral gene product encoded by each mRNA and the dashed lines show the alternative splicing of the IAV M and NS transcripts, as well as the IBV NS transcript. Red circles represent the 5′ M7pppG cap, black lines denote the 10–13 nucleotide, host-derived primers that are obtained by the cap-snatching mechanism of the viral polymerase. A(n) corresponds to the 3′ poly-A tail produced by reiterative stuttering of the viral polymerase. The smaller mRNAs (empty boxes) represent transcripts that encode nonessential accessory proteins found in many strains, whereas those that are less prevalent (PB2-S1, M42, and NS3) are not illustrated (6–11). (C) Diagram of an influenza A or B virus. The viral membrane proteins HA, NA, and M2 are shown, along with the eight viral ribonucleoproteins (vRNPs), and the matrix protein M1 that supports the viral envelope. To highlight the vRNP components, the illustration beneath the virus is not to scale. A single vRNA gene segment is shown wrapped around multiple nucleoprotein (NP) copies with the conserved promoter regions in the 5′ and 3′ UTRs forming a helical hairpin, which is bound by a single heterotrimeric viral RNA-dependent RNA polymerase (PB1, PB2, and PA). (D) Top view of an influenza virus cross-section showing the vRNP “1 + 7” configuration. vRNPs are depicted with black circles as it is not known if the positioning of a particular vRNP is conserved or interchangeable."

## Paramyxoviridae

Paramyxoviridae is a family of negative-strand RNA viruses in the order Mononegavirales. Vertebrates serve as natural hosts. Diseases associated with this family include measles, mumps, and respiratory tract infections. The family has four subfamilies, 17 genera, and 78 species, three genera of which are unassigned to a subfamily.
Morbillivirus measles (MeV), also called measles virus (MV), is a Negative-sense single-stranded RNA virus, enveloped, non-segmented RNA virus of the genus Morbillivirus within the family Paramyxoviridae.
This thin-section transmission electron micrograph (TEM, on the top right) revealed the ultrastructural appearance of a single virus particle, or “virion”, of measles virus. The measles virus is a paramyxovirus, of the genus Morbillivirus. It is 100-200 nm in diameter, with a core of single-stranded RNA, and is closely related to the rinderpest and canine distemper viruses. Two membrane envelope proteins are important in pathogenesis. They are the F (fusion) protein, which is responsible for fusion of virus and host cell membranes, viral penetration, and hemolysis, and the H (hemagglutinin) protein, which is responsible for adsorption of virus to cells. There is only one antigenic type of measles virus. Although studies have documented changes in the H glycoprotein, these changes do not appear to be epidemiologically important (i.e., no change in vaccine efficacy has been observed).
Prior to 1963, almost everyone got measles; it was an expected life event. Each year in the U.S. there were approximately 3 to 4 million cases and an average of 450 deaths, with epidemic cycles every 2 to 3 years. More than half the population had measles by the time they were 6 years old, and 90 % had the disease by the time they were 15. This indicates that many more cases were occurring than were being reported. However, after the vaccine became available, the number of measles cases dropped by 98 % and the epidemic cycles drastically diminished.
Measles virus is rapidly inactivated by heat, light, acidic pH, ether, and trypsin. It has a short survival time (<2 hours) in the air, or on objects and surfaces.
This 1976 negative stained transmission electron micrograph (TEM, second down on the right) depicted the ultrastructural features displayed by the mumps virus (Orthorubulavirus mumps, synonym Rubulavirus mumps).

## Picornaviridae

The three species of Enterovirus (rhinovirus) (A, B, and C) include around 160 recognized types of human rhinovirus that differ according to their surface proteins (serotypes).
When a cluster of nurses developed a mild respiratory illness, Winston Price, from the Johns Hopkins University, took nasal passage samples and isolated the first rhinovirus, which he called the JH virus, named after Johns Hopkins. His findings were published in 1956.
The seasonality may be due to the start of the school year in the Southern Hemisphere in January, yet colds are still predominant in autumn & winter and to people spending more time indoors thereby increasing the chance of transmission of the virus. Lower ambient temperatures, especially outdoors, may also be factor given that rhinoviruses preferentially replicate at 32 °C (89 °F) as opposed to 37 °C (98 °F).
A poliovirus, the causative agent of polio (also known as poliomyelitis), is a serotype of the species Enterovirus C, in the family of Picornaviridae. There are three poliovirus serotypes: types 1, 2, and 3.

## Poxviridae

Diseases associated with this genus include smallpox, cowpox, horsepox, camelpox, and monkeypox.
The most widely known member of the genus is Variola virus, which causes smallpox, eradicated globally by 1977, through the use of Vaccinia virus as a vaccine, where the most recently described species is the Alaskapox virus, first isolated in 2015.
Predicting the phylogeny by sequence or by gene content produces somewhat different results:
Orthopoxvirus phylogeny :
| By sequence | By gene content | Genus species | Common name |
| Ectromelia virus | Ectromelia virus | Orthopoxvirus ectromelia | mousepox |
| Cowpox virus, Germany and Brighton | Cowpox virus | Orthopoxvirus cowpox | cowpox |
| Taterapox virus, Camelpox virus, Variola virus | Horsepox | | |
| Monkeypox virus | Vaccinia, including rabbitpox |
| Cowpox virus, GRI strain | Variola virus |
| Vaccinia virus, including rabbitpox and horsepox | Taterapox virus, Camelpox virus, Monkeypox virus |
Some of the differences in the two trees are attributed to the procedure of passage in producing vaccinia strains. The MVA (Ankara) strain in this regard has a lot of gene loss related to in vitro passage, and horsepox being a vaccinia strain found in a natural outbreak has less.
Based on the genome organisation and DNA replication mechanism it seems that phylogenetic relationships may exist between the rudiviruses (Rudiviridae) and the large eukaryal DNA viruses: the African swine fever virus (Asfarviridae), Chlorella viruses (Phycodnaviridae) and poxviruses (Poxviridae).
Quokkapox virus (QPV), also known as quokka poxvirus, marsupial papillomavirus, or marsupialpox virus is a DNA virus#Group I: dsDNA viruses which is the cause of quokka pox. It is unclear whether this virus is its own species or a member of another species. It primarily infects the quokka, which is one of only four Macropodidae (macropodid) marsupials to get pox lesions. The lesions can mainly be seen on the tail, and can be up to 5 centimetres (2.0 in) in diameter.
Because the quokka host primarily lives on isolated islands in Western Australia, the range of the virus is limited as well. It was first described in 1972 from samples taken on Rottnest Island.