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Mokola virus (MOKV) is an
RNA virus An RNA virus is a virus characterized by a ribonucleic acid (RNA) based genome. The genome can be single-stranded RNA (ssRNA) or double-stranded (Double-stranded RNA, dsRNA). Notable human diseases caused by RNA viruses include influenza, SARS, ...
related to
rabies virus Rabies virus (''Lyssavirus rabies'') is a neurotropic virus that causes rabies in animals, including humans. It can cause violence, hydrophobia, and fever. Rabies transmission can also occur through the saliva of animals and less commonly throu ...
that has been sporadically isolated from mammals across sub-Saharan Africa. The majority of isolates have come from domestic cats exhibiting symptoms characteristically associated to
rabies virus Rabies virus (''Lyssavirus rabies'') is a neurotropic virus that causes rabies in animals, including humans. It can cause violence, hydrophobia, and fever. Rabies transmission can also occur through the saliva of animals and less commonly throu ...
infection. As of 2021, there have been two confirmed cases of Mokola virus infection in humans, of which one was fatal. The
rabies vaccine The rabies vaccine is a vaccine used to prevent rabies. There are several rabies vaccines available that are both safe and effective. Vaccinations must be administered prior to rabies virus exposure or within the Latent period (epidemiology), l ...
does not confer cross-protective immunity to Mokola virus, and no other known treatment for MOKV exists.


Classification

Mokola virus (MOKV) is a member of the genus ''
Lyssavirus ''Lyssavirus'' (from the Greek ''lyssa'' "rage, fury, rabies" and the Latin '' vīrus'') is a genus of RNA viruses in the family ''Rhabdoviridae'', order '' Mononegavirales''. Mammals, including humans, can serve as natural hosts. The genus ...
'', which belongs to the family ''
Rhabdoviridae ''Rhabdoviridae'' is a family of negative-strand RNA viruses in the order ''Mononegavirales''. Vertebrates (including mammals and humans), invertebrates, plants, fungi and protozoans serve as natural hosts. Diseases associated with member virus ...
''. MOKV is one of four
lyssavirus ''Lyssavirus'' (from the Greek ''lyssa'' "rage, fury, rabies" and the Latin '' vīrus'') is a genus of RNA viruses in the family ''Rhabdoviridae'', order '' Mononegavirales''. Mammals, including humans, can serve as natural hosts. The genus ...
es found in Africa. The other three viruses are the classic
rabies virus Rabies virus (''Lyssavirus rabies'') is a neurotropic virus that causes rabies in animals, including humans. It can cause violence, hydrophobia, and fever. Rabies transmission can also occur through the saliva of animals and less commonly throu ...
, Duvenhage virus and Lagos bat virus.


Emergence

MOKV was first isolated in Nigeria, in 1968, from three
shrew Shrews ( family Soricidae) are small mole-like mammals classified in the order Eulipotyphla. True shrews are not to be confused with treeshrews, otter shrews, elephant shrews, West Indies shrews, or marsupial shrews, which belong to dif ...
s (''
Crocidura The genus ''Crocidura'' is one of nine genera of the shrew subfamily Crocidurinae. Members of the genus are commonly called white-toothed shrews or musk shrews, although both also apply to all of the species in the subfamily. With over 180 sp ...
'' species) found in the Mokola forest, Ibadan, Oyo State, Nigeria. The virus was shown to be morphologically and serologically related to
rabies virus Rabies virus (''Lyssavirus rabies'') is a neurotropic virus that causes rabies in animals, including humans. It can cause violence, hydrophobia, and fever. Rabies transmission can also occur through the saliva of animals and less commonly throu ...
. Since the initial isolation of MOKV, the virus has been mainly isolated in domestic cats and small mammals in sub-Saharan Africa. There have been two recorded cases of human infection with MOKV, with both instances occurring in Nigeria. Both cases involved young Nigerian females. The first patient, who had been suffering from a
fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
and
convulsions A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is often used as a synony ...
, recovered fully from infection. The second case, which occurred in 1972, involved a 6-year-old girl who had been suffering from
drowsiness Somnolence (alternatively sleepiness or drowsiness) is a state of strong desire for sleep, or sleeping for unusually long periods (compare hypersomnia). It has distinct meanings and causes. It can refer to the usual state preceding falling asleep ...
. The second patient ultimately suffered from paralysis and a terminal
coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to Nociception, respond normally to Pain, painful stimuli, light, or sound, lacks a normal Circadian rhythm, sleep-wake cycle and does not initiate ...
as a result of the MOKV infection. The origin of the MOKV in both human cases of MOKV infection remains unidentified.


Genome and structure

The MOKV
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
consists of a non-segmented, single-stranded,
negative-sense In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of amino acids. Depending on the context, ...
RNA Ribonucleic acid (RNA) is a polymeric molecule that is essential for most biological functions, either by performing the function itself (non-coding RNA) or by forming a template for the production of proteins (messenger RNA). RNA and deoxyrib ...
molecule of 11,939
nucleotides Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
in length. It is estimated that 90.3% of the MOKV genome consists of protein-encoding or signal-encoding sequences. The genome encodes five
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
s: matrix protein M;
transmembrane A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently u ...
glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
G;
nucleoprotein Nucleoproteins are proteins conjugated with nucleic acids (either DNA or RNA). Typical nucleoproteins include ribosomes, nucleosomes and viral nucleocapsid proteins. Structures Nucleoproteins tend to be positively charged, facilitating inte ...
N;
phosphoprotein A phosphoprotein is a protein that is posttranslationally modified by the attachment of either a single phosphate group, or a complex molecule such as 5'-phospho-DNA, through a phosphate group. The target amino acid is most often serine, threonin ...
P; and the
RNA-dependent RNA polymerase RNA-dependent RNA polymerase (RdRp) or RNA replicase is an enzyme that catalyzes the self-replication, replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand Complementarity (molecular biology), compleme ...
L. MOKV is an enveloped virus, with the envelope lined with spikes consisting of the viral protein G. MOKV exhibits the 'bullet-shaped' morphology that is characteristic of members of the ''
Rhabdoviridae ''Rhabdoviridae'' is a family of negative-strand RNA viruses in the order ''Mononegavirales''. Vertebrates (including mammals and humans), invertebrates, plants, fungi and protozoans serve as natural hosts. Diseases associated with member virus ...
'' family.


Evolution

This virus appears to have evolved between 279 and 2,034 years before the present.


Transmission

The human cases of human MOKV infection have demonstrated the
zoonotic A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a virus, bacterium, parasite, fungi, or prion) that can jump from a non-human vertebrate to a human. When h ...
potential of MOKV, but as a
natural reservoir In Infection, infectious disease ecology and epidemiology, a natural reservoir, also known as a disease reservoir or a reservoir of infection, is the population of organisms or the specific environment in which an infectious pathogen naturally li ...
has not yet been identified, transmission of MOKV is poorly understood. Considering the MOKV isolates from small mammals and domestic cats; it has been suggested that small mammals, which are preyed upon by domestic cats, may be the natural MOKV reservoir. Unlike other ''
lyssavirus ''Lyssavirus'' (from the Greek ''lyssa'' "rage, fury, rabies" and the Latin '' vīrus'') is a genus of RNA viruses in the family ''Rhabdoviridae'', order '' Mononegavirales''. Mammals, including humans, can serve as natural hosts. The genus ...
es'', MOKV is able to replicate inside
mosquito Mosquitoes, the Culicidae, are a Family (biology), family of small Diptera, flies consisting of 3,600 species. The word ''mosquito'' (formed by ''Musca (fly), mosca'' and diminutive ''-ito'') is Spanish and Portuguese for ''little fly''. Mos ...
cells ''in vitro'', suggesting that
insects Insects (from Latin ') are hexapod invertebrates of the class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body (head, thorax and abdomen), three pairs of jointed ...
may be implicated in MOKV transmission.


Pathology

Symptoms provoked by MOKV infection are similar to the symptoms associated with
rabies virus Rabies virus (''Lyssavirus rabies'') is a neurotropic virus that causes rabies in animals, including humans. It can cause violence, hydrophobia, and fever. Rabies transmission can also occur through the saliva of animals and less commonly throu ...
infection, such as
fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...
and
headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...
. Ultimately, both MOKV and
rabies virus Rabies virus (''Lyssavirus rabies'') is a neurotropic virus that causes rabies in animals, including humans. It can cause violence, hydrophobia, and fever. Rabies transmission can also occur through the saliva of animals and less commonly throu ...
infection can lead to death by
encephalitis Encephalitis is inflammation of the Human brain, brain. The severity can be variable with symptoms including reduction or alteration in consciousness, aphasia, headache, fever, confusion, a stiff neck, and vomiting. Complications may include se ...
. The similarity between the symptoms associated with MOKV and
rabies virus Rabies virus (''Lyssavirus rabies'') is a neurotropic virus that causes rabies in animals, including humans. It can cause violence, hydrophobia, and fever. Rabies transmission can also occur through the saliva of animals and less commonly throu ...
may be the reason why there are so few case records of MOKV infection, as MOKV infection might be falsely diagnosed as
rabies virus Rabies virus (''Lyssavirus rabies'') is a neurotropic virus that causes rabies in animals, including humans. It can cause violence, hydrophobia, and fever. Rabies transmission can also occur through the saliva of animals and less commonly throu ...
infection. There is one significant difference between the symptoms observed in domestic cats infected with MOKV and those with
rabies virus Rabies virus (''Lyssavirus rabies'') is a neurotropic virus that causes rabies in animals, including humans. It can cause violence, hydrophobia, and fever. Rabies transmission can also occur through the saliva of animals and less commonly throu ...
. MOKV-infected domestic cats do not demonstrate the unprovoked aggressive behaviour typically associated with
rabies virus Rabies virus (''Lyssavirus rabies'') is a neurotropic virus that causes rabies in animals, including humans. It can cause violence, hydrophobia, and fever. Rabies transmission can also occur through the saliva of animals and less commonly throu ...
-infected mammals.


Treatment and prevention

At present, there is no medical or veterinary vaccine that protects against MOKV infection. It has long been established that, in spite of the relatedness between MOKV and
rabies virus Rabies virus (''Lyssavirus rabies'') is a neurotropic virus that causes rabies in animals, including humans. It can cause violence, hydrophobia, and fever. Rabies transmission can also occur through the saliva of animals and less commonly throu ...
, immunisation with the
rabies vaccine The rabies vaccine is a vaccine used to prevent rabies. There are several rabies vaccines available that are both safe and effective. Vaccinations must be administered prior to rabies virus exposure or within the Latent period (epidemiology), l ...
does not confer protection from MOKV infection. Isolation of MOKV from a number of domestic cats vaccinated with the
rabies vaccine The rabies vaccine is a vaccine used to prevent rabies. There are several rabies vaccines available that are both safe and effective. Vaccinations must be administered prior to rabies virus exposure or within the Latent period (epidemiology), l ...
has demonstrated this. In order to neutralize
rabies virus Rabies virus (''Lyssavirus rabies'') is a neurotropic virus that causes rabies in animals, including humans. It can cause violence, hydrophobia, and fever. Rabies transmission can also occur through the saliva of animals and less commonly throu ...
, the
rabies vaccine The rabies vaccine is a vaccine used to prevent rabies. There are several rabies vaccines available that are both safe and effective. Vaccinations must be administered prior to rabies virus exposure or within the Latent period (epidemiology), l ...
targets the
transmembrane A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently u ...
glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
G on the
viral envelope 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 en ...
. Variation in the
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
sequences of the antigenic domain III within protein G between rabies virus and MOKV has rendered the
rabies vaccine The rabies vaccine is a vaccine used to prevent rabies. There are several rabies vaccines available that are both safe and effective. Vaccinations must be administered prior to rabies virus exposure or within the Latent period (epidemiology), l ...
ineffective against MOKV infection.


References

{{Use dmy dates, date=April 2017 Lyssaviruses