18 June 2016

Lecture #20: The RNA-CONTAINING VIRUSES

************  PICORNAVIRUS  ************

Characteristics of the virus:

1.       They are 18–30 nm in diameter and are icosahedral in shape.
2.       They are positive stranded RNA viruses.
3.       It causes disease ranging from CNS infection, febrile illness with rash, conjunctivitis, herpangina, heart and lung infection to hepatitis.
4.       They are the smallest RNA virus

Classification of Picornavirus

                Genus                                  Main syndromes
               
                Enterovirus                       Infection of the CNS, skeletal muscles, skin and mucous membranes;
                                                                Hepatitis A
                Rhinovirus                         Common colds
                Apthovirus                         Foot and mouth disease
                Cardiovirus                        Encephalitis and myocarditis in rodents


THE ENTEROVIRUS

                Enterovirus infecting humans:

                Group                                 Number of serotypes

                Poliovirus                                          3
                Coxsackie A                                       23          
                Coxsackie B                                       6
                Echovirus                                           31
                Enterovirus                                       5 (numbered 68 – 72)

                Disease associated with Enterovirus:

1.      Poliomyelitis

a.       Incubation period: 7–14 days

b.       Types of illness produced:

(1)  Minor illness due to viremia

(2)  Major illness heralded by meningitic phase. The onset of the illness is abrupt with headache, fever, and vomiting and neck stiffness. Minor patients’ exhibits paralysis already. Paralysis of the lower motor neuron type with flaccidity of affected muscles. In bulbar, poliomyelitis, involvement of cranial nerves results in paralysis of the pharynx bringing difficulty with respiration.

c.       Mode of transmission: fecal–oral route

d.       The poliovirus replicates in the lymphoid tissue of the pharynx and gut including Peyer’s patches. The viremic phase brings lytic infection of neurons causing paralysis. The anterior horn cells of the spinal cord are the worst affected causing limb paralysis.

e.       Other abnormalities produced:

(1)  Inflammatory reactions
(2)  Perivascular infiltration with lymphocytes (cuffing)
(3)  Microglial proliferation
(4)  Edema

Syndromes caused by Coxsackievirus, Echovirus and Enterovirus 70 & 71

                                                                Coxsackievirus                                                 Enterovirus
System affected                               A             B             Echovirus           Type 70               Type 71

1.       CNS
a.       Meningitis                          +             +             +                                                             +
b.       Paralytic disease             +             +             +                                                             +
c.       Encephalitis                      +             ++           ++                                                           ++
d.       Encephalomyelitis                         +
2.       Heart / Skeletal                        +             ++           +
3.       GI tract                                                                        ++
4.       Respiratory tract                    ++           ++           +                                                             +
5.       Skin, mucous membranes
a.       Rashes                                  +                             +
b.       Herpangina                        ++
c.       Hand, foot & mouth
disease                                 ++           +                                                                             ++
6.       Conjunctiva                               +                                                             ++
7.       Pancreas                                                     +
8.       Perinatal infection                 +             ++           +

·         Type 72 is Hepatitis A

Laboratory diagnosis:

1.       Human or monkey cell culture and observe for:

a.       Cytopathogenic effect within 2–3 days
b.       Rounding of cells
c.       Complete destruction of monolayer

2.       Neutralization test using LBM (Lim, Benyesh, Melnick) pool of reference sera. This contains antibodies to some viruses but not others. By noting which pools do or do not neutralize infectivity, it is possible to identify the virus in the specimens.

3.       Cell culture inoculation in newborn mice of clinical specimens in which Coxsackie A and B virus induce flaccid and spastic paralysis respectively.

4.       IgM antibody test using ELISA

5.       Polymerase chain reaction

Treatment, epidemiology and control:

1.       None of the enteroviruses, including poliovirus is susceptible to chemotherapy and there are no vaccines except for poliomyelitis. Control therefore depends on hygienic measures:
a.       Proper management of food, water supplies and sewage.
b.       Handwashing and correct disposal or disinfection of potentially contaminated materials.
2.       Most enterovirus survive well in moist or wet environments and are thus readily transmitted via the fecal–oral route as described for polioviruses and are therefore most prevalent in hot countries and during the summer months in temperate zones.
3.       The transmission of infections acquired by the respiratory or conjunctival routes is facilitated by overcrowding.
4.       Most infections are subclinical.
5.       Enterovirus infections occur predominantly in children, some, particularly those of the CNS, affect boys more often, or more severely, than girls.
6.       Epidemics of some – but not all – enterovirus occur periodically.

THE HEPATITIS A VIRUS (HAV)

                Characteristics of the virus:

1.       It has a cubic symmetry and in 27 nm in diameter
2.       The nucleic acid is a single stranded RNA with positive polarity
3.       It has an incubation period of 2–6 weeks

Pathogenesis:

1.       Clinical illness usually starts with few days of malaise loss of appetite, vague abdominal discomfort and fever. The urine then becomes dark and feces pale.
2.       Jaundice becomes apparent after the initial symptom, first in the sclera and then in the skin; if severe, it may be accompanied by itching.
3.       The patient starts to feel better within the next week or so and the jaundice disappears within a month.
4.       HAV first replicates in the gut; there is then a viremic phase during which, presumably, the virus gets into the liver. Further replication in the hepatocytes causes necrosis of these cells, which tends to be more pronounced the center of the lobules. There is proliferation of Kuppfer and other endothelial cells and are secondary periportal inflammations with mononuclear cells.


************  REOVIRUS  ************

Characteristics of the virus:

1.       “REO” stands for Respiratory Enteric Orphan.
2.       They are wheel–like in appearance. The capsid has a double–shell and is 70 nm in diameter, some smaller, single–shelled particles may also be seen. In most virions a number of “spokes” radiate from a central “hub,” although some appear empty by negative contrast staining. The cores appear to be icosahedral.
3.       They differ from all other RNA viruses in that their genomes are double–stranded. Electrophoresis of extracted RNA shoes that they are also divided into 10–12 segments of varying size, coding for a similar number of structural and non–structural proteins.
4.       The electrophoretic migration pattern of the nucleic acid differs between strains and is used by some to define “electropherotypes,” which do not correspond with the serotypes but which may be useful for epidemiological studies.

Two genus of the Reoviruses:

1.       Rotavirus
a.       It has an incubation period of 2–4 days; the characteristic syndrome comprises vomiting, diarrhea and fever, but silent infections also occur. Dehydration must be dealt promptly.
b.       It primarily attaches the columnar epithelium at the apices of the villi of the duodenum and upper ileum; the loss of these cells results in malabsorption. Regeneration from the bases of the villi is normally rapid after the acute attack.

2.       Orbivirus
a.       They are transmitted from small rodents by ticks. They cause febrile illnesses, often with meningitis or meningoencephalitis:
(1)  Colorado tick fever
(2)  Kemerovo viruses

Laboratory diagnosis:

1.       For rotavirus – trypsis treated monkey kidney cell culture.
2.       Test for IgG

************  BUNYAVIRUS  ************

Characteristics of the virus:

1.       They have a spherical particle containing single negative–sense RNA genome that is segmented.
2.       They have a lipid containing envelope and measures 90–100 nm. The envelope has two glycoproteins in the lipid bilayer and surface projections (10 nm) of glycopeptides clustered to form hollow cylinders.
3.       All members of the family are arthropod–transmitted except for Hantavirus which is rodent excreta transmitted.

The four genus of Bunyaviridae:

1.       Orthobunyavirus – California encephalitis, Oropouche fever
2.       Phlebovirus – Sandfly (Phlebotomus) fever, Rift Valley Fever
3.       Nairovirus – Crimean–Congo hemorrhagic fever
4.       Hantavirus – Epidemic hemorrhagic nephropathy

Diseases associated with Bunyavirus:

1.      California encephalitis

Characterized by severe bifrontal headache, fever of 38–40oC, sometimes vomiting, lethargy and convulsions. Less frequently, there is only aseptic meningitis.

Histopathological changes include neuronal degeneration and patchy inflammation with perivascular cuffing and edema in the cerebral cortex and meninges. This is transmitted by Aedes triseriatus and small mammals such as squirrels and rabbits.

2.      Oropouche Fever

Characterized by febrile illness (especially in Brazil). Three types of syndromes have been associated: febrile illness, febrile illness with rash, meningitis or meningismus. Many patients become severely ill, some to the point of prostration. The disease may be confused with malaria or other febrile conditions. The incubation period varies from 4 to 8 days. Fever, chills, severe headache, myalgias, arthralgia, dizziness and photophobia are the most common clinical manifestations. This is transmitted by Culicoides paraensis (main vector) and Culicoides quiquefasciatus.

Two cycles of Oropouche virus:

a.       Jungle cycle (vector unknown) – responsible for maintaining the virus in nature, where primates, sloths and possibly certain species of wild birds are implicated as vertebrate hosts.

b.       Urban cycle – humans maybe infected and once infected, probably serve as an amplifying host of the virus among hetophagus insects.

3.      Epidemic Hemorrhagic Nephropathy

This is spread via rodent excreta. The signs are those of a viral hemorrhagic fever accompanied by renal pain and proteinuria.

4.      Rift Valley Fever Virus – is the causative agent of Rift Valley Fever, a viral disease that can cause mild to severe symptoms. The mild symptoms may include: fever, muscle pains, and headaches which often last for up to a week. The severe symptoms may include: loss of sight, beginning three weeks after the infection, infection of the brain causing severe headache and confusion, and bleeding together with liver problems which may occur within the first few days. Those who have bleeding have a chance of death as high as 50%. It is spread by either touching infected animal blood, breathing in the air around an infected animal being butchered, drinking raw milk from an infected animal or the bite of infected mosquite (Culex tritaeniorhynchus and Aedes vexans).

5.      Crimean–Congo hemorrhagic fever

This is transmitted to human tick (Hyalomma marginatum marginatum and Rhipicephalus sanguineus)


************  TOGAVIRUS AND FLAVIVIRUS  ************

Characteristics of the virus:

1.       The virions are spherical and enveloped, 40–90 nm in diameter. The nucleocapsid has icosahedral symmetry and contains a single molecule of positive–sense RNA.

2.       The envelope contains one (flavirus) or two (togaviruses) E proteins that mediate fusion of viral cellular membranes, releasing RNA into the cell cytoplasm; here it functions as mRNA, directing synthesis of a single polyprotein that is processed to form the structural protein of the virus.

3.       Togavirus bud from the external plasma membrane of the cell in much the same was as influenza viruses, whereas flavivirus but internally into cytoplasmic vacuoles.

4.       Both viruses are arbovirus. Arbovirus is a term used to refer to a group of viruses that are transmitted by arthropod vectors. The word arbovirus is an acronym (ARthropod–BOrne virus). Symptoms of arbovirus infection generally occur 3–15 days after exposure to the virus and last 3 or 4 days. The most common clinical features of infection are fever, headache, and malaise, but encephalitis and hemorrhagic fever may also occur.


Family                                                Disease                                              Vector

Flaviviridae                                       Yellow Fever                                    Aedes aegypti
                                                                Dengue (4 Types)                           Aedes aegypti
                                                                Omsk                                                    Ondatra zibethicus
                                                                Japanese Encephalitis                   Culex tritaeniorhynchus
                                                                West Nile                                            Culex tarsalis
                                                                Zika                                                       Aedes aegypti

Togaviridae                                       O’nyong’nyong                                 Anopheles funestus
                                                                Chikungunya                                     Aedes albopictus
                                                                Ross river                                           Aedes camptorhynchus

Diseases associated with Flavirus and Togavirus:


1.       Dengue Virus – is the causative agent of dengue fever. It is transmitted to human Aedes mosquito. Five serotypes of the virus have been identified.

2.       Japanese Encephalitis Virus – is the causative agent of Japanese Encephalitis. Domestic pigs and wild birds (especially herons) are reservoir of the virus; transmission to human may cause severe symptoms. Amongst the important vectors of this disease are the mosquitoes Culex tritaeniorhynchus and Culex vishnui

3.       West Nile Virus – transmitted to humans by mosquitoes. The important mosquito vectors vary according to geographical area; in the Eastern United States (Culex pipens), in Midwest and West United States (Culex tarsalis) and in Southeast United States (Culex quinquefasciatus)

4.       Yellow Fever Virus – transmitted to human through the bite of Aedes aegypti. Yellow fever is an acute viral disease. Symptoms include fever, chills, loss of appetite, nausea, muscle pains particularly in the back and headaches. Symptoms typically improve within five days. In some people within a day of improving, the fever comes back, abdominal pain occurs and liver damage begins causing yellow skin. If this occurs, the risk of bleeding and kidney problems is also increased.

5.       Zika VIrus – transmitted to human by Aedes aegypti and Aedes albopictus. Symptoms may include fever, red eyes, joint pain, headache, and a maculopapular rash. Symptoms general last less than seven days. Infection during pregnancy causes microcephaly and other brain malformations in some babies. Infections in adults have been linked to Guillain–Barre syndrome.

6.       Omsk Hemorrhagic Fever Virus – transmitted to humans via contaminated water or an infected tick. The main hosts of OHFV are rodents (Ondatra zibethicus).

7.       O’nyong’nyong Virus – transmitted to human by bite of Anopheles funestus and Anopheles gambiae. The name originated for the Nilotic language of Uganda and Sudan which means “weakening of the joints.”

8.       Chikungunya – transmitted to humans by the bite Aedes albopictus and Aedes aegypti. Characteristics symptoms include sudden onset with high fever, joint pain, and rash.

9.       Ross River Virus – previously known to cause a disease known as “epidemic polyarthritis.” It is transimitted to humans by Aedes camptorhynchus.



************  ARENAVIRUSES  ************

These are group of virus that infects rodents and occasionally humans. It is also been discovered to infect snakes. The disease is transferred to human via rodents.

LCM viruses

Lymphocytic choriomeningitis (LCM) is a rodent–borne viral infections disease that presents as aseptic meningitis, encephalitis or meningoencephalitis. LCMV is naturally spread by the common house mouse (Mus musculus). The virus seems to be relatively resistant to drying and therefore humans can become infected by inhaling infectious aerolized particles of rodent urine, feces or saliva, by ingesting food contaminated with virus, by contamination of mucous membranes with infected body fluids, or by directly exposing cuts or other open wounds to virus–infected blood.

Lassa Fever

The primary animal host of Lassa virus is Mastomys natalensis, an animal found in
sub–Saharan Africa which transmits the disease to human through aerolized excreta. Lassa Fever occurs commonly in West Africa. Outbreaks of the disease have been observed in Nigeria, Liberia, Sierra Leone, Guinea and Central African Republic.

Junin virus

The causative agent of Argentine Hemorrhagic Fever (AHF). AHF leads to severe compromise of the vascular, neurological and immune systems and has a mortality rate between 20 and 30%. Symptoms of the disease are conjunctivitis, purpura, petechial and occasionally sepsis.

The natural host of Junin virus are rodents, particularly, Mus musculus, Calomys spp. and Akodon azarae. Direct rodent–to–human transmission only takes place when a person makes direct contact with the excrement of an infected rodent; this can occur by ingestion of contaminated food or water, inhalation of particles in urine or direct contact of an open would with rodent feces.

Machupo Virus

                The vector is the vesper mouse Calomys callosus, a rodent indigenous to Northern Bolivia.
                Infected animals are asymptomatic and shed the virus in excreta, thereby infecting humans.
                The disease is known as Bolivian Hemorrhagic Fever (BHF) or Black typhus or Ordog Fever. 


************ CORONAVIRUS  ************

The genomic size of coronaviruses ranges from approximately 26 to 32 kilobases, the largest for RNA virus. The name “coronavirus” is derived from the Latin “corona” meaning crown or halo and refers to the characteristic appearance of virions under electron microscopy with a fringe of large, bulbous surface projections creating an image reminiscent of a royal crown or the solar corona. Most of the coronaviruses produce respiratory syndrome.


                Human coronavirus 229E
                Human coronavirus OC43
                SARS- CoV
                Human coronavirus NL63
                Human coronavirus HKU1
                Middle East Respiratory Syndrome coronavirus


************  RETROVIRUSES  ************

Human T–lymphotropic virus

Causative agent of Adult T–cell leukemia/lymphoma and HTLV–1 associated myelopathy / tropical spastic paraperesis (HAM / TSP), a medical condition that causes weakness, muscle spasms and sensory disturbance. Just like HIV, it is acquired by sexual contact, blood transfusion, needle sharing and breast feeding.     

Human Immunodeficiency Virus (HIV)

                The causative agent of Acquired Immune Deficiency Syndrome (AIDS). HIV is a member of the genus Lentivirus, part of the Retroviridae family.




Human Foamy Virus (HFV)

HFV is a retrovirus and specifically belongs to the genera Spumavirus. The foamy viruses derive their name from the characteristic “foamy” appearance of the cytopathic effect (CPE) induced in the cells.


************  ORTHOMYXOVIRUSES  ************
               
Bourbon virus

A virus discovered in 2014 from a man from Bourbon Country, Kansas, USA. It was caused by genus Thogotoviridae. It is transmitted to human tick bite.

                Influenza Virus B & Influenza Virus C – causative agent of Viral Flu.  

Quaranfil virus

Quaranjaviruses infect both arthropod and vertebrate hosts. The most common arthropod hosts are species of soft–bodied (Argasidae family) ticks. Most members cannot infect mosquito cell lines in the laboratory. Infection in humans generally appears to be asymptomatic and has occasionally been reported to be associated with mild fever.


************  PARAMYXOVIRUSES  ************

Human Parainfluenza Virus (hPIV)

Human parainfluenza viruses commonly cause upper and lower respiratory illness in infants and young children, but anyone can get infected. After you get infected, it takes about 2 to 7 days before symptoms develop. Symptoms of “upper” respiratory illness include: fever, runny nose and cough. Symptoms of “lower” respiratory illness include: croup (infection of the vocal cords, windpipe and bronchial tubes), bronchitis, bronchiolitis and pneumonia. Young children are more susceptible to the disease.
               
Human metapneumovirus

The second cause of lower respiratory infection in young children. Compared with respiratory syncytial virus, infection with human metapneumovirus tends to occur in slightly older children and to produce disease that is less severe.
               
************  RHABDOVIRUSES  ************

Rabies Virus

Caused by the genus Lyssavirus. Rabies virus is a neurotropic virus that causes rabies in human and animals. Infection with rabies virus is characterized by violent movements, uncontrolled excitement, fear of water, inability to move parts of the body, confusion and loss of consciousness. Once symptoms appear, the result is nearly always death.




************  ASTROVIRUSES  ************

Astrovirus

Recognized to cause gastroenteritis in children and adults. The main symptoms are diarrhea, followed by nausea, vomiting, fever, malaise and abdominal pain. Some research studies have shown that the duration of the symptoms are approximately three to four days. Astrovirus infection is not usually a severe situation and only in some rare causes leads to dehydration. Infected people do not need hospitalization because symptoms reduce by themselves after a short time.


************  HEPEVIRUSES  ************

Hepatitis E Virus is transmitted by fecal–oral route.  Although Hepatitis E often causes an acute and self–limiting infection with low mortality rates, it bears a high risk in developing chronic hepatitis in immunocompromised patients with substantial mortality rates. Organ transplant recipients who receive immunosuppressive medication to prevent rejection are thought to be the main population at risk for chronic hepatitis E. Pregnant woman, especially those in the third semester, suffers an elevated mortality rate from the disease by 20%.


************  FILOVIRUSES  ************

Ebola virus

Ebola Virus is known to cause severe and often fatal hemorrhagic fever (Ebola Virus Disease) in human. The natural reservoir of Ebola virus is believed to be fruit bats and it is primarily transmitted between humans and from animals to humans through body fluids. Ebola virus outbreaks tend to occur when temperatures are lower and humidity is higher than the usual for Africa. Even after a person recovers from the acute phase of the disease, Ebola virus survives for months in certain organs such as the eyes and testes.

Marburg virus



Marburg Virus disease is clinically indistinguishable from Ebola Virus Disease. The most important indicator that may lead to the suspicion of MVD at clinical examination is the medical history of the patient. 



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