ARBOVIRUSES. DNA-VIRUSES: HERPESVIRUSES. ADENOVIRUSES ARBOVIRUSES. DNA-VIRUSES: HERPESVIRUSES....

ARBOVIRUSES.ARBOVIRUSES.

DNA-VIRUSES: DNA-VIRUSES: HERPESVIRUSES. HERPESVIRUSES. ADENOVIRUSES ADENOVIRUSES

By as. Kuchmak O.B.

Microbiology, virology, immunology department

Common and important herpesviruses Common and important herpesviruses of humans include herpes simplex of humans include herpes simplex virus types 1 and 2, varicella-zoster virus types 1 and 2, varicella-zoster virus, Epstein-Barr (EB) virus, and virus, Epstein-Barr (EB) virus, and cytomegalovirus.cytomegalovirus.

Properties of the Viruses: All herpesviruses have a core of double-stranded DNA surrounded by a protein coat that exhibits icosahedral symmetry. The nucleocapsid is surrounded by an envelope.

HERPES SIMPLEX:HERPES SIMPLEX:

Human Herpesvirus 1 (Herpes Labialis) &Human Herpesvirus 2 (Herpes Genitalis).

Infection with herpes simplex virus may take several clinical forms. The infection is most often inapparent. The usual clinical manifestation is a vesicular eruption of the skin or mucous membranes. Infection is sometimes seen as severe keratitis, meningoencephalitis, and a disseminated illness of the newborn.

Cytopathic effect (infected cells develop intranuclear acidophilic inclusion and then undergo necrosis )

Herpes labialis (cold sores, herpes febrilis).

This is the most common recurrent disease produced by type 1. Clusters of localized vesicles occur, usually at the mucocutaneous junction of the lips. The vesicle ruptures, leaving a painful ulcer that heals without scarring. The lesions may recur, repeatedly and at various intervals of time, in the same location. The permanent site of latent herpes simplex virus is the trigeminal ganglion.

Herpes labialis

Keratoconjunctivitis.Keratoconjunctivitis.

The initial infection with herpesvirus may be in the eye, producing severe keratoconjunctivitis. Recurrent lesions of the eye appear as dendritic keratitis or corneal ulcers or as vesicles on the eyelids. With recurrent keratitis, there may be progressive involvement of the corneal stroma, with permanent opacification and blindness.

Genital herpes (herpes progenitalis).

Genital herpes is characterized by vesiculoulcerative lesions of the penis of the male or the cervix, vulva, vagina, and perineum of the female. The lesions are more severe during primary infection and may be associated with fever, malaise, and inguinal lymphadenopathy. Type 2 virus remains latent in lumbar and sacral ganglia.

NeonatalNeonatal herpes.herpes. Herpesvirus type 2 may be transmitted to the newborn during birth by contact with herpetic lesions in the birth canal. The spectrum of illness produced in the newborn appears to vary from subclinical or local to severe generalized disease with a fatal outcome. Severely affected infants who survive may have permanent brain damage.

The virus may be isolated from herpetic lesions (skin, cornea, or brain).

The appearance of typical cytopathic effects in cell culture suggests the presence of herpesvirus in 18-36 hours. Scrapings or swabs from the base of early herpetic lesions contain multinucleated giant cells.

Serology: The agent is then identified by neutralization test or immunofluorescence staining with specific antiserum. Antibodies appear in 4-7 days; can be measured by NT, IHT, CFT, RIA and reach a peak in 2-4 weeks.

Laboratory Diagnosis

HV, immune fluorescence test

Varicella (chickenpox) is a mild, highly infectious disease, chiefly of children, characterized clinically by a vesicular eruption of the skin and mucous membranes. The causative agent is indistinguishable from the virus of zoster.

Zoster (shingles) is a sporadic, incapacitating disease of adults (rare in children) that is characterized by an inflammatory reaction of the posterior nerve roots and ganglia, accompanied by crops of vesicles (like those of varicella) over the skin supplied by the affected sensory nerves.

VARICELLA-ZOSTER VIRUS VARICELLA-ZOSTER VIRUS (Human Herpesvirus 3)(Human Herpesvirus 3)

(Chickenpox, Herpes Zoster, Shingles, (Chickenpox, Herpes Zoster, Shingles, Zona)Zona)

Both diseases are caused by the same virus. Varicella is the acute disease that follows primary contact with the virus, whereas zoster is the response of the partially immune host to a reactivation of varicella virus present in latent form in sensory ganglia.

VARICELLA-ZOSTER VIRUS VARICELLA-ZOSTER VIRUS (Human Herpesvirus 3)(Human Herpesvirus 3)

(Chickenpox, Herpes Zoster, Shingles, (Chickenpox, Herpes Zoster, Shingles, Zona)Zona)

Pathogenesis & PathologyPathogenesis & Pathology. Varicella: The route of infection is probably the mucosa of the upper respiratory tract. The virus probably circulates in the blood and localizes in the skin. Swelling of epithelial cells, ballooning degeneration, and the accumulation of tissue fluids result in vesicle formation. In nuclei of infected cells, particularly in the early stages, eosinophilic inclusion bodies are found.

Varicella virus, pathogenesispathogenesis

VaricellVaricellaa

ChickenpoxChickenpox

Pathogenesis & Pathology.

Zoster: In addition to skin lesions — histopathologically identical with those of varicella — there is an inflammatory reaction of the dorsal nerve roots and sensory ganglia. Often only a single ganglion may be involved. As a rule, the distribution of lesions in the skin corresponds closely to the areas of innervation from an individual dorsal root ganglion. There is cellular infiltration, necrosis of nerve cells, and inflammation of the ganglion sheath.

ZosterZoster

ShinglShingleses

CYTOMECALOVIRUSCYTOMECALOVIRUS (Human Herpesvirus 5)

Cytomegalic inclusion disease is a generalized infection of infants caused by intrauterine or early postnatal infection with the cytomegaloviruses. The disease causes severe congenital anomalies. Cytomegalovirus can be found in the cervix of up to 10% of healthy women. Cytomegalic inclusion disease is characterized by large intranuclear inclusions that occur in the salivary glands, lungs, liver, pancreas, kidneys, endocrine glands, and occasionally, the brain. Most fatalities occur in children under 2 years of age. Inapparent infection is common during childhood and adolescence. Severe cytomegalovirus infections are frequently found in adults receiving immunosuppressive therapy.

Cytomegalovirus Inclusion Diseases. Electron micrograph of a single animal cell infected with the cytomegalovirus.The intranuclear inclusion body has a typical” owl-eyed” apearence.

Cytomegalovirus can cause persistent infection in various tissues, including those of the salivary glands, breasts, kidneys, endocervix, seminal vesicles and peripheral blood leukocytes. This persistent infection leads to chronic viral excretion by the involved organ. Transmission of virus is through contact with infected secretions. The average incubation period is four to six weeks.

It should also be noted that the kidneys of organ donors can be a source of cytomegalovirus for the recipient, and that peripheral blood leukocytes have been implicated in the transmission of cytomegalovirus via blood transfusion.

Pathogenesis.

Cytomegalovirus infection can result in one of three distinct clinical syndromes. Congenital cytomegalovirus infection: hepatospleno-megaly, retinitis, a petechial/purpuric skin rash, and involvement of the central nervous system (ventriculo-megaly, intracranial calcifications, etc).

Clinical Manifestations.Clinical Manifestations.

Mononucleosis syndrome (fever, malaise, atypical lymphocytosis, pharyngitis and, rarely, cervical adenopathy or hepatitis) Third clinical entity is cytomegalovirus infection in severely immunocompromised individuals. In these patients, infection can involve the lungs, gastrointestinal tract, liver, retina, and central nervous system

Clinical Manifestations.Clinical Manifestations.

EB (Epstein-Barr) virus is the causative agent of infectious mononucleosis and has been associated with Burkitt's lymphoma and nasopharyngeal carcinoma.

EB HERPESVIRUS (Human Herpesvirus 4).

Epidemiology. Epstein-Barr virus is transmitted by intimate contact.Pathogenesis. Epstein-Barr virus is tropic for B-lymphocytes.

Infectious mononucleosis

Nasopharyngeal carcinoma

Burkitt's lymphoma

Oncogenic Properties:Oncogenic Properties:

Herpesviruses have been linked with malignant diseases in humans : herpes simplex virus type 2 with cervical and vulvar carcinoma; EB virus with Burkilt 's lymphoma of African children and with nasopharyngeal carcinoma.

acute respiratory disease, pharyngoconjunctival fever, nonstreptococcal exudative pharyngitis, and primary atypical pneumonia

Laboratory Diagnosis.

The viruses have been recovered from throat swabs, conjunctival swabs, rectal swabs, stools of patients with acute pharyngitis and conjunctivitis, and urine of patients with acute hemorrhagic cystitis. Virus isolations from the eye are obtained mainly from patients with conjunctivitis.

Laboratory Diagnosis.

The viruses are isolated by inoculation of tissue cultures of human cells in which characteristic cytopathic changes are produced.

A new serotype that has not been isolated in cell cultures can be detected by direct examination of fecal extracts by electron microscopy or by enzyme-linked immunosorbent assay.

Serology. In most cases, the neutralizing antibody titer of infected persons shows a 4-fold or greater rise against the type recovered from the patient in NT. The CF test, using the common antigen, is an easily applied method for detecting infection by any member of the group.A sensitive radioimmunoassay can measure serum antibody to type 5 fiber antigen.

Laboratory Diagnosis.

The arthropod-borne viruses, or arboviruses, are a group of infectious agents that are transmitted by blood-sucking arthropods from one vertebrate

host to another.

They can multiply in the tissues of the arthropod without evidence of disease or damage. The vector acquires a lifelong infection through the ingestion of blood from a viremic vertebrate.

All arboviruses have an RNA genome, and most have a lipid-containing envelope and consequently are inactivated by ether or sodium deoxycholate.

Togaviridae Genus AlphavirusFlaviviridae Genus FlavivirusBunyaviridae Genus BunyavirusReoviridae Genus OrbivirusRhabdoviridae Genus VesiculovirusArenaviridae Genus ArenavirusNodaviridae

Current taxonomic status of some arboviruses

Structures of Alphaviruses

Principal medically important alphaviruses

Virus Antigenic Clinical

Syndrome Vector Host Distributio

n

Eastern equine

encephalitis

Encephalitis (EEE)

Mosquito Birds Americas

Western equine

encephalitis

Encephalitis (WEE)

Mosquito Birds North America

Venezuelan equine

encephalitis

Febrile illness,

encephalitis (VEE)

Mosquito Rodents, horses

Americas

Virus Antigenic Clinical

Syndrome Vector Host Distributio

n

Chikunguny (CHIK)

Febrile illness, rash,

arthralgia

Mosquito Primates, humans

Africa, India,

Southeast Asia

O’nyong-nyong (ONN)

Febrile illness, rash,

arthralgia

Mosquito Primates Africa

Sindbisc (SIN)

Febrile illness, rash,

arthralgia

Mosquito Birds Nothern Europe,

Africa, Asia, Australia

Semliki Forest

Febrile illness, rare encephalitis

Mosquito Birds Africa

FIGURE Alphavirus transmission. Virus abbreviations: Chik, chickungunya; RR, Ross River; May, Mayaro; ONN, O'nyong-nyong; SIN, Sindbis; EEE, eastern equine encephalitis; VEE, Venezuelan equine encephalitis.

Pathogenesis of alphaviruses

The rubella virus is a member of the genus Rubivirus in the family Togaviridae.

Rubellaviruses

(German measles) is a common mild disease characterized by a rash. It affects children and adolescents worldwide and can also affect young adults.

When rubella virus infects susceptible women early in pregnancy, it may be transmitted to the fetus and may cause birth defects. Therefore, accurate diagnosis is critical in pregnancy.

Rubella

FIGURE. Clinical findings, virus shedding, and serologic response in postnatally acquired rubella.

Abnormalities Associated with Congenital Rubella Syndrome

Type of defects Examples

Ocular defects CataractsMicrophthalmiaGlaucomaRetinitis

Heart defects Patent ductus arteriosus Atrial septal defectVentricular septal defectPeripheral pulmonic artery stenosis

Hearing impairment Sensorineural deafness

Abnormalities Associated with Congenital Rubella Syndrome

Type of defects Examples

Central nervous system

Mental retardationMeningoencephalitisProgressive rubella panencephalitis (rare)Microcephaly

Other Growth retardationRadiolucent borne diseaseHepatosplenomegalyHemathologic abnormalities:Thrombocytopenia, purpuraPneumonitisEndocrine dysfunction:Insulin dependent diabetes mellitus, thyroididtis

Cataract

Glaucoma

Structure of Flaviviruses

Virus Antigenic Clinical

Syndrome

Vector Host Distribution

Dengue (DEN)

Febrile illness, rash, hemorrhagic fever, shock syndrome

Mosquito Humans Tropics, worldwide

Yellow fever (YF)

Hemorrhagic fever,

hepatitis

Mosquito Primates, humans

Africa, South America

St. Louis encephalitis (SLE)

Encephalitis Mosquito Birds Americas

Principal medically important flaviviruses

Virus Antigenic Clinical

Syndrome

Vector Host Distribution

Japanese encephalitis

(JE)

Encephalitis Mosquito Pigs, birds India, China, Japan,

South-East Asia

West Nile Febrile illness

Mosquito Birds Africa, Middle East,

Europe

Tick-borne encephalitis (TBE)

Encephalitis Tick Rodent Europa, Asia

Principal medically important flaviviruses

Virus Antigenic Clinical

Syndrome

Vector Host Distribution

Omsk hemorrhagic

fever

Hemorrhagic fever

Tick Muskrats Siberia

Kyasanur Forest disease (KFD)

Hemorrhagic fever

Tick Rodents India primates

Principal medically important flaviviruses

Tick-born encephalitis virus

Human infection with both mosquito-borne and tick-borne flaviviruses is initiated by deposition of virus through the skin via the saliva of an infected arthropod (Fig).

Figure. Pathogenesis of flaviviruses.

Yellow fever

Dengue fever

Bunyaviridae is a family of arthropod-borne or rodent-borne, spherical, enveloped RNA viruses. Bunyaviruses are responsible for a number of febrile diseases in humans and other vertebrates. They have either a rodent host or an arthropod vector and a vertebrate host.

Genus and Group

Virus Disease

Vector Distribution

Bunyavirus

Bunyamwera

Bunyamwera Fever Mosquito Africa

Bwamba Bwamba Fever , Rash

Mosquito Africa

California California encephalitis

Encepha-litis

Mosquito North America

Simbu Shuni Fever Mosquito Africa, Asia

Human diseases Caused by Viruses

of the Family Bunyaviridae

Human diseases Caused by Viruses of the Family Bunyaviridae

Genus and Group

Virus Disease Vector Distribution

Phlebovirus

Phlebovirus fever

Alenquer Fever Unknown South America

Naples Fever Sand fly Europe, Asia, Africa

Rift Valley Fever

Fever, encephalitis, hemorrhagic

fever, blindness

Mosquito Africa

Sicilian Fever Sand fly Europe, Africa, Asia

Human diseases Caused by Viruses of the Family Bunyaviridae

Genus and Group

Virus Disease Vector Distribution

Nairovirus

Crimean-Congo

Crimean-Congo

hemorrhagic fever

Hemorrhagic fever

Tick Africa, Asia

Nairobi sheep disease

Nairobi sheep

disease

Fever Tick Africa, Asia

Human diseases Caused by Viruses of the Family Bunyaviridae

Genus and Group

Virus Disease Vector Distribution

Hantavirus

Hataan Hantaan HFPS (hantavirus pulmonary syndrom)

Rodent Asia

Puumala HFPS Rodent Asia

Sequl HFPS Rodent Asia, Europe

Human diseases Caused by Viruses of the Family Bunyaviridae

Genus and Group

Virus Disease Vector Distribution

Genus unassigned

Bangui Fever, rash Unknown Africa

Bhanja Fever, encephalitis

Tick Africa, Europa, Asia

Issk-kul Fever Tick Asia

Kasokero Fever Unknown Africa

Nyando Fever Mosquito Africa

Tataguine Fever Mosquito Africa

Wanowrie Fever, hemorrhage

Tick Middle East, Asia

FIGURE. Pathogenesis of bunyavirus infections. Humans are dead-end hosts of most bunyaviruses; however, the blood of Crimean-Congo hemorrhagic fever patients may be highly infectious.

Signs of Crimean-Congo Hemorrhagic Fever