| Influenza virus life cycle |
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Viral entry is the earliest stage of infection in the viral life cycle, as the virus comes into contact with the host cell and introduces viral material into the cell. The major steps involved in viral entry are shown below. [1] Despite the variation among viruses, there are several shared generalities concerning viral entry. [2]
How a virus enters a cell is different depending on the type of virus it is. A virus with a nonenveloped capsid enters the cell by attaching to the attachment factor located on a host cell. It then enters the cell by endocytosis or by making a hole in the membrane of the host cell and inserting its viral genome. [2]
Cell entry by enveloped viruses is more complicated. Enveloped viruses enter the cell by attaching to an attachment factor located on the surface of the host cell. They then enter by endocytosis or a direct membrane fusion event. The fusion event is when the virus membrane and the host cell membrane fuse together allowing a virus to enter. It does this by attachment – or adsorption – onto a susceptible cell; a cell which holds a receptor that the virus can bind to. The receptors on the viral envelope effectively become connected to complementary receptors on the cell membrane. This attachment causes the two membranes to remain in mutual proximity, favoring further interactions between surface proteins. This is also the first requisite that must be satisfied before a cell can become infected. Satisfaction of this requisite makes the cell susceptible. Viruses that exhibit this behavior include many enveloped viruses such as HIV and herpes simplex virus. [2]
These basic ideas extend to viruses that infect bacteria, known as bacteriophages (or simply phages). Typical phages have long tails used to attach to receptors on the bacterial surface and inject their viral genome.
Prior to entry, a virus must attach to a host cell. Attachment is achieved when specific proteins on the viral capsid or viral envelope bind to specific proteins called receptor proteins on the cell membrane of the target cell. A virus must now enter the cell, which is covered by a phospholipid bilayer, a cell's natural barrier to the outside world. The process by which this barrier is breached depends upon the virus. Types of entry are:
Through the use of green fluorescent protein (GFP), virus entry and infection can be visualized in real-time. Once a virus enters a cell, replication is not immediate and indeed takes some time (seconds to hours). [3] [4]
The most well-known example is through membrane fusion. In a number of viruses with a viral envelope, viral receptors attach to the receptors on the surface of the cell and secondary receptors may be present to initiate the puncture of the membrane or fusion with the host cell. Following attachment, the viral envelope fuses with the host cell membrane, causing the virus to enter. Viruses that enter a cell in this manner included HIV, KSHV [5] [6] [7] [8] and herpes simplex virus. [9]
In SARS-CoV-2 and similar viruses, entry occurs through membrane fusion mediated by the spike protein, either at the cell surface or in vesicles. Research efforts have focused on the spike protein's interaction with its cell-surface receptor, angiotensin-converting enzyme 2 (ACE2). The evolved, high level of activity to mediate cell to cell fusion has resulted in an enhanced fusion capacity. [10] Inhibition of SARS-2 infection targets the spike proteins that harbor the capacity for membrane fusion. [11] Vaccinations are based on the inhibition of spike (S) glycoprotein mediating the fusion of the virus and its host cell membranes. [12] The fusion mechanism is also studied as a potential target for antiviral development. [13]
Viruses with no viral envelope enter the cell generally through endocytosis; they are ingested by the host cell through the cell membrane. Cells can take in resources from the environment outside of the cell, and these mechanisms may be used by viruses to enter a cell in the same manner as ordinary resources. Once inside the cell, the virus leaves the vesicle by which it was taken up in order to gain access to the cytoplasm. Examples include the poliovirus, hepatitis C virus, [14] and foot-and-mouth disease virus. [15]
Many enveloped viruses, such as SARS-CoV-2, also enter the cell through endocytosis. Entry via the endosome guarantees low pH and exposure to proteases which are needed to open the viral capsid and release the genetic material inside. Further, endosomes transport the virus through the cell and ensure that no trace of the virus is left on the surface, which could be a substrate for immune recognition. [16]
A third and more specific example, is by simply attaching to the surface of the cell via receptors on the cell, and injecting only its genome into the cell, leaving the rest of the virus on the surface. This is restricted to viruses in which only the genome is required for infection of a cell (for example positive-strand RNA viruses because they can be immediately translated) and further restricted to viruses that actually exhibit this behavior. The best studied example includes the bacteriophages; for example, when the tail fibers of the T2 phage land on a cell, its central sheath pierces the cell membrane and the phage injects DNA from the head capsid directly into the cell. [17]
Once a virus is in a cell, it will activate formation of proteins (either by itself or using the host) to gain full control of the host cell, if it is able to. Control mechanisms include the suppression of intrinsic cell defenses, suppression of cell signaling and suppression of host cellular transcription and translation. Often, it is these cytotoxic effects that lead to the death and decline of a cell infected by a virus.
A cell is classified as susceptible to a virus if the virus is able to enter the cell. After the introduction of the viral particle, unpacking of the contents (viral proteins in the tegument and the viral genome via some form of nucleic acid) occurs as preparation of the next stage of viral infection: viral replication.
Measles morbillivirus(MeV), also called measles virus (MV), is a single-stranded, negative-sense, enveloped, non-segmented RNA virus of the genus Morbillivirus within the family Paramyxoviridae. It is the cause of measles. Humans are the natural hosts of the virus; no animal reservoirs are known to exist.
The term viral protein refers to both the products of the genome of a virus and any host proteins incorporated into the viral particle. Viral proteins are grouped according to their functions, and groups of viral proteins include structural proteins, nonstructural proteins, regulatory proteins, and accessory proteins. Viruses are non-living and do not have the means to reproduce on their own, instead depending on their host cell's machinery to do this. Thus, viruses do not code for most of the proteins required for their replication and the translation of their mRNA into viral proteins, but use proteins encoded by the host cell for this purpose.
Φ6 is the best-studied bacteriophage of the virus family Cystoviridae. It infects Pseudomonas bacteria. It has a three-part, segmented, double-stranded RNA genome, totalling ~13.5 kb in length. Φ6 and its relatives have a lipid membrane around their nucleocapsid, a rare trait among bacteriophages. It is a lytic phage, though under certain circumstances has been observed to display a delay in lysis which may be described as a "carrier state".
Pestivirus is a genus of viruses, in the family Flaviviridae. Viruses in the genus Pestivirus infect mammals, including members of the family Bovidae and the family Suidae. There are 11 species in this genus. Diseases associated with this genus include: hemorrhagic syndromes, abortion, and fatal mucosal disease.
A viral envelope is the outermost layer of many types of viruses. It protects the genetic material in their life cycle when traveling between host cells. Not all viruses have envelopes. A viral envelope protein or E protein is a protein in the envelope, which may be acquired by the capsid from an infected host cell.
Simian foamy virus (SFV) is a species of the genus Spumavirus that belongs to the family of Retroviridae. It has been identified in a wide variety of primates, including prosimians, New World and Old World monkeys, as well as apes, and each species has been shown to harbor a unique (species-specific) strain of SFV, including African green monkeys, baboons, macaques, and chimpanzees. As it is related to the more well-known retrovirus human immunodeficiency virus (HIV), its discovery in primates has led to some speculation that HIV may have been spread to the human species in Africa through contact with blood from apes, monkeys, and other primates, most likely through bushmeat-hunting practices.
Viral shedding is the expulsion and release of virus progeny following successful reproduction during a host cell infection. Once replication has been completed and the host cell is exhausted of all resources in making viral progeny, the viruses may begin to leave the cell by several methods.
Corticovirus is a genus of viruses in the family Corticoviridae. Corticoviruses are bacteriophages; that is, their natural hosts are bacteria. The genus contains two species. The name is derived from Latin cortex, corticis. However, prophages closely related to PM2 are abundant in the genomes of aquatic bacteria, suggesting that the ecological importance of corticoviruses might be underestimated. Bacteriophage PM2 was first described in 1968 after isolation from seawater sampled from the coast of Chile.
Mason-Pfizer monkey virus (M-PMV), formerly Simian retrovirus (SRV), is a species of retroviruses that usually infect and cause a fatal immune deficiency in Asian macaques. The ssRNA virus appears sporadically in mammary carcinoma of captive macaques at breeding facilities which expected as the natural host, but the prevalence of this virus in feral macaques remains unknown. M-PMV was transmitted naturally by virus-containing body fluids, via biting, scratching, grooming, and fighting. Cross contaminated instruments or equipment (fomite) can also spread this virus among animals.
Major capsid protein VP1 is a viral protein that is the main component of the polyomavirus capsid. VP1 monomers are generally around 350 amino acids long and are capable of self-assembly into an icosahedral structure consisting of 360 VP1 molecules organized into 72 pentamers. VP1 molecules possess a surface binding site that interacts with sialic acids attached to glycans, including some gangliosides, on the surfaces of cells to initiate the process of viral infection. The VP1 protein, along with capsid components VP2 and VP3, is expressed from the "late region" of the circular viral genome.
West Nile virus (WNV) is a single-stranded RNA virus that causes West Nile fever. It is a member of the family Flaviviridae, from the genus Flavivirus, which also contains the Zika virus, dengue virus, and yellow fever virus. The virus is primarily transmitted by mosquitoes, mostly species of Culex. The primary hosts of WNV are birds, so that the virus remains within a "bird–mosquito–bird" transmission cycle. The virus is genetically related to the Japanese encephalitis family of viruses. Humans and horses both exhibit disease symptoms from the virus, and symptoms rarely occur in other animals.
Pneumoviridae is a family of negative-strand RNA viruses in the order Mononegavirales. Humans, cattle, and rodents serve as natural hosts. Respiratory tract infections are associated with member viruses such as human respiratory syncytial virus. There are five species in the family which are divided between the genera Metapneumovirus and Orthopneumovirus. The family used to be considered as a sub-family of Paramyxoviridae, but has been reclassified as of 2016.
Bovine foamy virus (BFV) is a ss(+)RNA retrovirus that belongs to the genus spumaviridae. Spumaviruses differ from the other six members of family retroviridae, both structurally and in pathogenic nature. Spumaviruses derive their name from spuma the latin for "foam". The 'foam' aspect of 'foamy virus' comes from syncytium formation and the rapid vacuolization of infected cells, creating a 'foamy' appearance.
Middelburg virus (MIDV) is an alphavirus of the Old World Group that has likely endemic and zoonotic potential. It is of the viral family Togaviridae. It was isolated from mosquitos in 1957 in South Africa, MDIV antigens have now been found in livestock, horses, and humans.
Avian metaavulavirus 2, formerly Avian paramyxovirus 2, is a species of virus belonging to the family Paramyxoviridae and genus Metaavulavirus. The virus is a negative strand RNA virus containing a monopartite genome. Avian metaavulavirus 2 is one of nine species belonging to the genus Metaavulavirus. The most common serotype of Avulavirinae is serotype 1, the cause of Newcastle disease (ND). Avian metaavulavirus 2 has been known to cause disease, specifically mild respiratory infections in domestic poultry, including turkeys and chickens, and has many economic effects on egg production and poultry industries. The virus was first isolated from a strain in Yucaipa, California in 1956. Since then, other isolates of the virus have been isolated worldwide.
Mammalian orthoreovirus (MRV) is a double-stranded RNA virus. It is a part of the family Reoviridae, as well as the subfamily Spinareovirinae. As seen in the name, the Mammalian Ortheoreovirus infects numerous mammalian species and vertebrates which serve as natural hosts. Some diseases that occur as a result of this virus or are associated with this virus include mild upper respiratory illness, and gastrointestinal illness. Examples of these are: upper respiratory tract syndromes, gastroenteritis, biliary atresia, obstructive hydrocephalus, jaundice, alopecia, conjunctivitis, and ‘oily hair’ associated with steatorrhea.
The woolly monkey hepatitis B virus (WMHBV) is a viral species of the Orthohepadnavirus genus of the Hepadnaviridae family. Its natural host is the woolly monkey (Lagothrix), an inhabitant of South America categorized as a New World primate. WMHBV, like other hepatitis viruses, infects the hepatocytes, or liver cells, of its host organism. It can cause hepatitis, liver necrosis, cirrhosis, and hepatocellular carcinoma. Because nearly all species of Lagothrix are threatened or endangered, researching and developing a vaccine and/or treatment for WMHBV is important for the protection of the whole woolly monkey genus.
Ghanaian bat henipavirus (also known Kumasi virus belongs to the genus Henipavirus in the family Paramyxoviridae. Human infections are caused by zoonotic events where the virus crosses over from another animal species. Therefore, humans are not the innate host for this virus family but instead become infected by peripheral viral reservoirs such as bats and other carriers of the virus. When these virus are spread to humans through zoonotic events they have been found to be one of the most deadly viruses with the capability to infect humans, with mortality rates between 50 and 100%. Therefore, these viruses have been classified as a biosafety level four virus with regards to its pathogenesis when it infects humans.
Rio Negro virus is an alphavirus that was first isolated in Argentina in 1980. The virus was first called Ag80-663 but was renamed to Rio Negro virus in 2005. It is a former member of the Venezuelan equine encephalitis complex (VEEC), which are a group of alphaviruses in the Americas that have the potential to emerge and cause disease. Río Negro virus was recently reclassified as a distinct species. Closely related viruses include Mucambo virus and Everglades virus.
Spike (S) glycoprotein is the largest of the four major structural proteins found in coronaviruses. The spike protein assembles into trimers that form large structures, called spikes or peplomers, that project from the surface of the virion. The distinctive appearance of these spikes when visualized using negative stain transmission electron microscopy, "recalling the solar corona", gives the virus family its main name.
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| Viral life cycle | ||
| Genetics | ||
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