Mokola Virus
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''Mokola lyssavirus'', commonly called Mokola virus (MOKV), is an
RNA virus An RNA virus is a virusother than a retrovirusthat has ribonucleic acid (RNA) as its genetic material. The nucleic acid is usually single-stranded RNA ( ssRNA) but it may be double-stranded (dsRNA). Notable human diseases caused by RNA viruses ...
related to
rabies virus Rabies virus, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...
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, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...
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 a number of rabies vaccines available that are both safe and effective. They can be used to prevent rabies before, and, for a period of time, after exposure to the rabies virus, ...
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, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...
, Duvenhage virus and
Lagos bat virus ''Lagos bat lyssavirus'', formerly Lagos bat virus (LBV) is a ''Lyssavirus'' of southern and central Africa that causes a rabies-like illness in mammals. It was first isolated from a fruit bat (''Eidolon helvum'') from Lagos Island, Nigeria in 19 ...
.


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 different fa ...
s (''
Crocidura The genus ''Crocidura'' is one of nine genus, 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 18 ...
'' 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, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...
. 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, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
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 sometimes used as a s ...
, 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 respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...
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 In the fields of molecular biology and genetics, 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 ge ...
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 essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
molecule of 11,939
nucleotides Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules w ...
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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s: matrix protein M;
transmembrane A transmembrane protein (TP) 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 frequentl ...
glycoprotein Glycoproteins are proteins which contain oligosaccharide 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 as glycos ...
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 replication of RNA from an RNA template. Specifically, it catalyzes synthesis of the RNA strand complementary to a given RNA template. This is in contrast to t ...
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 bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human. ...
potential of MOKV, but as a
natural reservoir In 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 lives and rep ...
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 (or mosquitos) are members of a group of almost 3,600 species of small flies within the family Culicidae (from the Latin ''culex'' meaning " gnat"). The word "mosquito" (formed by ''mosca'' and diminutive ''-ito'') is Spanish for "li ...
cells ''in vitro'', suggesting that
insects Insects (from Latin ') are pancrustacean 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 j ...
may be implicated in MOKV transmission.


Pathology

Symptoms provoked by MOKV infection are similar to the symptoms associated with
rabies virus Rabies virus, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...
infection, such as
fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
and
headache Headache 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 in those with severe headaches. Headaches can occur as a result ...
. Ultimately, both MOKV and
rabies virus Rabies virus, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...
infection can lead to death by
encephalitis Encephalitis is inflammation of the brain. The severity can be variable with symptoms including reduction or alteration in consciousness, headache, fever, confusion, a stiff neck, and vomiting. Complications may include seizures, hallucinations, ...
. The similarity between the symptoms associated with MOKV and
rabies virus Rabies virus, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...
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, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...
infection. There is one significant difference between the symptoms observed in domestic cats infected with MOKV and those with
rabies virus Rabies virus, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...
. MOKV-infected domestic cats do not demonstrate the unprovoked aggressive behaviour typically associated with
rabies virus Rabies virus, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...
-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, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...
, immunisation with the
rabies vaccine The rabies vaccine is a vaccine used to prevent rabies. There are a number of rabies vaccines available that are both safe and effective. They can be used to prevent rabies before, and, for a period of time, after exposure to the rabies virus, ...
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 a number of rabies vaccines available that are both safe and effective. They can be used to prevent rabies before, and, for a period of time, after exposure to the rabies virus, ...
has demonstrated this. In order to neutralize
rabies virus Rabies virus, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...
, the
rabies vaccine The rabies vaccine is a vaccine used to prevent rabies. There are a number of rabies vaccines available that are both safe and effective. They can be used to prevent rabies before, and, for a period of time, after exposure to the rabies virus, ...
targets the
transmembrane A transmembrane protein (TP) 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 frequentl ...
glycoprotein Glycoproteins are proteins which contain oligosaccharide 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 as glycos ...
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. Numerous human pathogenic viruses in circulation are encase ...
. Variation in the
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
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 a number of rabies vaccines available that are both safe and effective. They can be used to prevent rabies before, and, for a period of time, after exposure to the rabies virus, ...
ineffective against MOKV infection.


References

{{Use dmy dates, date=April 2017 Lyssaviruses