Usutu virus
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Usutu virus (USUV) is a
flavivirus ''Flavivirus'' is a genus of positive-strand RNA viruses in the family ''Flaviviridae''. The genus includes the West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, Zika virus and several other viruses which may cau ...
belonging to the
Japanese encephalitis Japanese encephalitis (JE) is an infection of the brain caused by the Japanese encephalitis virus (JEV). While most infections result in little or no symptoms, occasional inflammation of the brain occurs. In these cases, symptoms may include he ...
complex, which is an emerging
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. ...
arbovirus Arbovirus is an informal name for any virus that is transmitted by arthropod vectors. The term ''arbovirus'' is a portmanteau word (''ar''thropod-''bo''rne ''virus''). ''Tibovirus'' (''ti''ck-''bo''rne ''virus'') is sometimes used to more sp ...
of concern because of its
pathogenicity In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a ge ...
to humans and its similarity in ecology with other emerging arboviruses such as
West Nile virus 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 v ...
. It mainly infects ''
Culex ''Culex'' is a genus of mosquitoes, several species of which serve as vectors of one or more important diseases of birds, humans, and other animals. The diseases they vector include arbovirus infections such as West Nile virus, Japanese encep ...
'' mosquitoes and birds; humans form a dead-end host. First identified in
South Africa South Africa, officially the Republic of South Africa (RSA), is the Southern Africa, southernmost country in Africa. It is bounded to the south by of coastline that stretch along the Atlantic Ocean, South Atlantic and Indian Oceans; to the ...
in 1959, the virus has caused outbreaks in birds across Europe since 1996. Nearly 50 cases in humans have been reported as of 2019, mainly in Europe. These are predominantly asymptomatic, but some people experience neurological symptoms.


History

USUV was first identified by Bruce McIntosh in '' Culex neavei'' mosquitoes in
South Africa South Africa, officially the Republic of South Africa (RSA), is the Southern Africa, southernmost country in Africa. It is bounded to the south by of coastline that stretch along the Atlantic Ocean, South Atlantic and Indian Oceans; to the ...
in 1959, and is named after the Usutu River. The virus was later identified in '' Mansonia aurites'' mosquitoes in Uganda. In 1996, USUV was identified outside Africa for the first time, causing significant mortality among
Old World blackbirds True thrushes are medium-sized mostly insectivorous or omnivorous birds in the genus ''Turdus'' of the wider thrush family, Turdidae. The genus name ''Turdus'' is Latin for "thrush". The term "thrush" is used for many other birds of the family Tu ...
in Italy. Only two human cases have been identified in Africa, in 1981 and 2004, with one benign and one severe case described. The first human case outside Africa was reported in Italy in 2009, where an
immunocompromised Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
patient was infected, causing encephalitis.


Virology

USUV has a diameter of 40–60 nm and is enveloped. The
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 g ...
is a +-sense, single-stranded RNA of 11,064 nucleotides with a 5′ N7-methylguanosine-triphosphate cap. There is one
open reading frame In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readin ...
, which encodes a 3434-
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 a ...
polyprotein. This is processed to generate eleven proteins: three structural and eight non-structural proteins. Replication occurs in the
cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
of the host cell.The virus has eight lineages, five in Europe and three in Africa.


Epidemiology and host range

USUV has been reported from several African countries including
Burkina Faso Burkina Faso (, ; , ff, 𞤄𞤵𞤪𞤳𞤭𞤲𞤢 𞤊𞤢𞤧𞤮, italic=no) is a landlocked country in West Africa with an area of , bordered by Mali to the northwest, Niger to the northeast, Benin to the southeast, Togo and Ghana to ...
,
Central African Republic The Central African Republic (CAR; ; , RCA; , or , ) is a landlocked country in Central Africa. It is bordered by Chad to the north, Sudan to the northeast, South Sudan to the southeast, the DR Congo to the south, the Republic of th ...
,
Cote d'Ivoire Ivory Coast, also known as Côte d'Ivoire, officially the Republic of Côte d'Ivoire, is a country on the southern coast of West Africa. Its capital is Yamoussoukro, in the centre of the country, while its largest city and economic centre i ...
,
Morocco Morocco (),, ) officially the Kingdom of Morocco, is the westernmost country in the Maghreb region of North Africa. It overlooks the Mediterranean Sea to the north and the Atlantic Ocean to the west, and has land borders with Algeria t ...
,
Nigeria Nigeria ( ), , ig, Naìjíríyà, yo, Nàìjíríà, pcm, Naijá , ff, Naajeeriya, kcg, Naijeriya officially the Federal Republic of Nigeria, is a country in West Africa. It is situated between the Sahel to the north and the Gulf o ...
,
Senegal Senegal,; Wolof: ''Senegaal''; Pulaar: 𞤅𞤫𞤲𞤫𞤺𞤢𞥄𞤤𞤭 (Senegaali); Arabic: السنغال ''As-Sinighal'') officially the Republic of Senegal,; Wolof: ''Réewum Senegaal''; Pulaar : 𞤈𞤫𞤲𞤣𞤢𞥄𞤲𞤣𞤭 ...
, South Africa,
Tunisia ) , image_map = Tunisia location (orthographic projection).svg , map_caption = Location of Tunisia in northern Africa , image_map2 = , capital = Tunis , largest_city = capital , ...
and
Uganda }), is a landlocked country in East Africa. The country is bordered to the east by Kenya, to the north by South Sudan, to the west by the Democratic Republic of the Congo, to the south-west by Rwanda, and to the south by Tanzania. The sou ...
, as well as from
Israel Israel (; he, יִשְׂרָאֵל, ; ar, إِسْرَائِيل, ), officially the State of Israel ( he, מְדִינַת יִשְׂרָאֵל, label=none, translit=Medīnat Yīsrāʾēl; ), is a country in Western Asia. It is situated ...
. Since 1996, it has also been found in European countries, including Austria, Belgium, Croatia, Czech Republic, France, Germany, Greece, Hungary, Italy, Serbia, Spain and Switzerland, and more recently the Netherlands, and was spreading across Europe in the late 2010s. Outbreaks are often simultaneous with those of the related ''
West Nile virus 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 v ...
''. USUV's host range includes primarily ''
Culex ''Culex'' is a genus of mosquitoes, several species of which serve as vectors of one or more important diseases of birds, humans, and other animals. The diseases they vector include arbovirus infections such as West Nile virus, Japanese encep ...
'' mosquitoes and birds. The main bird hosts are blackbirds (''Turdus merula''),
magpies Magpies are birds of the Corvidae family. Like other members of their family, they are widely considered to be intelligent creatures. The Eurasian magpie, for instance, is thought to rank among the world's most intelligent creatures, and is one ...
(''Pica pica'') and owls, including the
great grey owl The great grey owl (''Strix nebulosa'') (also great gray owl in American English) is a very large owl, documented as the world's largest species of owl by length. It is distributed across the Northern Hemisphere, and it is the only species in th ...
(''Strix nebulosa''). In addition to humans, the virus has been isolated from ''
Pipistrellus ''Pipistrellus'' is a genus of bats in the family Vespertilionidae and subfamily Vespertilioninae. The name of the genus is derived from the Italian word , meaning "bat" (from Latin "bird of evening, bat"). The size of the genus has been cons ...
'' bats, and anti-USUV antibodies have been found in horses, dogs, deer, wild boar, rodents and shrews. Humans and horses are dead-end hosts. The
vector Vector most often refers to: *Euclidean vector, a quantity with a magnitude and a direction *Vector (epidemiology), an agent that carries and transmits an infectious pathogen into another living organism Vector may also refer to: Mathematic ...
is one of several mosquitoes that bite birds, in Europe particularly ''
Culex pipiens ''Culex pipiens'', commonly referred to as the common house mosquito, is a species of mosquito. House mosquitoes are some of the most common mosquitoes in the United States. More specifically, ''Culex pipiens'' is considered as the northern hous ...
''. For example, a 2008–2009 survey of mosquitoes and birds in the
Emilia-Romagna egl, Emigliàn (man) egl, Emiglièna (woman) rgn, Rumagnòl (man) rgn, Rumagnòla (woman) it, Emiliano (man) it, Emiliana (woman) or it, Romagnolo (man) it, Romagnola (woman) , population_note = , population_blank1_title ...
region of Italy detected USUV in 89 ''C. pipiens'' pools and in 2 ''
Aedes albopictus ''Aedes albopictus'' (''Stegomyia albopicta''), from the mosquito (Culicidae) family, also known as the (Asian) tiger mosquito or forest mosquito, is a mosquito native to the tropical and subtropical areas of Southeast Asia. In the past few cen ...
'' pools, suggesting the possible involvement of ''A. albopictus'' in the virus cycle. The virus was also found in twelve wild birds, primarily Eurasian magpies (''P. pica''),
hooded crow The hooded crow (''Corvus cornix''), also called the scald-crow or hoodie, is a Eurasian bird species in the genus ''Corvus''. Widely distributed, it is found across Northern, Eastern, and Southeastern Europe, as well as parts of the Middle Eas ...
s (''Corvus cornix''), and Eurasian jays (''Garrulus glandarius''). In Africa multiple ''Culex'' species are involved, as well as several species of ''
Aedes ''Aedes'' is a genus of mosquitoes originally found in tropical and subtropical zones, but now found on all continents except perhaps Antarctica. Some species have been spread by human activity: '' Aedes albopictus'', a particularly invasive sp ...
'' and other mosquitoes.


Disease

Two cases of symptomatic infection in humans have been reported from Africa, with
fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...
and
skin rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...
but no neurological symptoms. In Europe, 46 infections were detected up to 2019; these were mainly asymptomatic, but neurological symptoms including encephalitis and
meningoencephalitis Meningoencephalitis (; from ; ; and the medical suffix ''-itis'', "inflammation"), also known as herpes meningoencephalitis, is a medical condition that simultaneously resembles both meningitis, which is an infection or inflammation of the menin ...
have been observed. The virus is highly pathogenic in birds, causing central nervous system symptoms, enlargement of the
liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
and
spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .
, and infiltration by inflammatory cells in a wide range of organs.


References

{{DEFAULTSORT:Usutu virus Encephalitis Viral infections of the central nervous system Flaviviruses Viral encephalitis