C hair of M icrobiology, V irology, and I mmunology. Adenoviruses Family. ADENOVIRUS (ADV). DNA viruses first isolated from adenoidal tissue in 1953 Family Adenoviridae Genus Mastadenovirus There names adenoid degeneration viruses adenoid-pharingeal conjunctival viruses
Chair of Microbiology, Virology, and Immunology
DNA viruses first isolated from adenoidal tissue in 1953
acute respiratory desease agents.
Non-enveloped DNA virus
70-90 nm in size
Linear ds DNA genome with core proteins
Dodecon: Hemagglutinin made up of 12 pentons
with their fibers.
ADENOVIRUS - Classification
Subgroups- 6 subgroups (A-F), based on hemagglutination
Serotypes- 1-49 (human)
Common serotypes:- 1-8, 11, 21, 35, 37, 40
Enteric Adenoviruses belong to subgroup F
Human Adenoviruses Types
Adenoviruses in the cells
Pathogenesis and Replication
Infects mucoepithelial cells of respiratory, GI and GU tracts
Enter via epithelium, replicate and spread to lymphoid tissue
Secondary involvement of viscera
Adenovirus-Host Cell Interaction
Military recruits ( 10% basic trainees in 1st week)
swimming pool users, hospitals,
residential institutions, day care settings
Direct and through poorly chlorinated water
Adenoviral serotypes and associated diseases
Remaining serotypes are infrequently isolated or not clearly associated with disease.
* Association with gastroenteritis not as firmly established as with types 40 and 41.
Early conjunctivitis (left) and Bilateral conjunctivitis (right)
Irritation, tearing, foreign-body sensation
Conjunctival injection, ecchymosis
Corneal injection (limbus)
Diffuse→focal epithelial keratitis
↓Visual acuity (subepithelial corneal opacities)
Ipsilateral pre-auricular lymphadenopathy
Acute hemorrhagic cystitis
Other Infections due to Adenovirus
pediatric – associated serotypes
Activated T cell infusion –
All herpesviruses have a core of double-stranded DNA surrounded by a protein coat that exhibits icosahedral symmetry and has 162 capsomeres. The nucleocapsid is surrounded by an envelope. The enveloped form measures 150-200 nm; the "naked" virion, 100 nm. The double-stranded DNA (MW 85-150xlO6) has a wide range of guanine + cytosine content in different herpesviruses, There is little DNA homology among different herpesviruses, except herpes simplex types 1 and 2.
Gammaherpesvirinae (EBV, HV-6, 7, 8 MDV):
In vitro viruses replicate in liphoblast cells, cause lytic infection in epithelioid cells fibroblasts.
Viruses have tropism both Т-, and В-lymphocytes, but as a rool infection process is stopped at prelytic stage, so productive cases are absent.
HERPES SIMPLEX (Human Herpesvirus 1 and 2)
(Herpes labialis, Herpes genitalis, and many other syndromes).
Infection with herpes simplex virus (herpesvirus hominis) 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.
Properties of the Virus. The envelope is derived from the nuclear membrane of the infected cell. It contains lipids, carbohydrate, and protein and is removed by ether treatment. The double-stranded DNA genome is linear (MW 85-106 x 106).
Types 1 and 2 show 50% sequence homology. Treatment with restriction endonucleases yields characteristically different cleavage patterns for type 1 and 2 viruses and even for different strains of each type. This "fingerprinting" of strains allows epidemiologic tracing of a given strain, whereas in the past, the ubiquitousness of herpes simplex virus made such investigations impossible.
Herpesvirus. Several proteins have been identified in the virion, The protein I is associated with the viral capsid; the glycoproteins present in bands 0, 2 -3, 8, and 9 (glycoproteins) are associated with the envelope; and a DNA-binding protein (band number 13) is associated with the internal core.
Chorionallantoic membrane (right) infected with Herpesvirus
The plaques produced by herpesvirus type 2 are larger than the tiny plaques produced by type 1 virus. The virus grows readily and produces plaques in almost any cell culture. Infected cells develop inclusion bodies and then undergo necrosis (cytopathic effect).
In Chinese hamster cells, which contain 22 chromosomes, the virus causes breaks in region 7 of chromosome No. 1 and in region 3 of the X chromosome. The Y chromosome is unaffected.
Viral cytopathogenic effect (right)
Differentiation of Types 1 and 2
Herpes simplex virus types 1 and 2 cross-react serologically but may be distinguished by a number of tests: (1) The use of type-specific antiserum prepared by adsorption of the viral antiserum with heterotypically infected cells or by inoculation of rabbits with individual type-specific proteins. (2) The greater temperature sensitivity of type 2 infectivity. (3) Preferential growth in different cell species. (4) Restriction enzyme patterns of virus DNA molecules. (5) Differences in the polypeptides produced by type 1 and type 2.
Oncogenic Properties: After inactivation of their lytic capabilities by ultraviolet irradiation or other means, herpesvirus types 1 and 2 can cause transformation of cultured hamster cells, which may induce tumours when inoculated into newborn hamsters. Viral genetic information can be demonstrated in the tumour cells.
Pathogenesis of herpetic infection
Herpesvirus Type 1
The clinical entities attributable to herpesvirus type 1 include the following:
1. Acute herpetic gingivostomatitis (aphthous stomatitis, Vincent's stomatitis). This is the most common clinical entity caused by primary infections with type 1 herpesvirus. It occurs most frequently in small children (1-3 years of age) and includes extensive vesiculoulcerative lesions of the mucous membranes of the mouth, fever, irritability, and local lymphadenopathy. The incubation period is short (about 3-5 days), and the lesions heal in 2-3 weeks.
2. Eczema herpeticum (Kaposi's varicelliform eruption). This is a primary infection, usually with herpesvirus type 1, in a person with chronic eczema. In this illness, there may be extensive vesiculation of the skin over much of the body and high fever. In rare instances, the illness may be fatal.
3. 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.
4. Encephalitis. A severe form of encephalitis may be produced by herpesvirus. In adults, the neurologic manifestations suggest a lesion in the temporal lobe. Pleocytosis (chiefly of lymphocytes) is present in the cerebrospinal fluid; however, definite diagnosis during the illness can usually be made only by isolation of the virus (or by demonstrating viral antigens by immunofluorescence) from brain tissue obtained by biopsy or at post-mortem. The disease carries a high mortality rate, and those who survive often have residual neurologic defects.
5. 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.
Herpesvirus Type 2
1. Genital herpes (herpes progenitalis): vesiculoulcerative lesions of the penis of the male or the cervix, vulva, vagina, and perineum of the female. The lesions may be associated with fever, malaise, and inguinal lymphadenopathy. In women with herpesvirus antibodies, only the cervix or vagina may be involved, and the disease may therefore be asymptomatic.
Type 2 virus remains latent in lumbar and sacral ganglia. Changing patterns of sexual behaviour are reflected by an increasing number of type 1 virus isolations from genital lesions and of type 2 from facial lesions, presumably as a result of oral-genital sexual activity.
HV, immune fluorescence test
VARICELLA-ZOSTER VIRUS (Human Herpesvirus 3)
VARICELLA (Chickenpox) ZOSTER (Herpes Zoster, Shingles, Zona)
Varicella (chickenpox) is a mild, highly infectious disease, chiefly of children, characterized clinically by a vesicular eruption of the skin and mucous membranes. However, in immunocompromised children the disease may be severe. 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.
Herpes zoster pathogenesis
CYTOMECALOVIRUS (Human Herpesvirus 5) (Cytomegalic Inclusion Disease)
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 in about 10,000 infants in the USA per year. Cytomegalovirus can be found in the cervix of up to 10% of healthy women.
Cytomegalovirus in the cells
Retina infected by Cytomegalofirus
EB HERPESVIRUS (Human Herpesvirus 4)
(Infectious Mononucleosis, Burkitt's Lymphoma,
EB (Epstein-Barr) virus is the causative agent of infectious mononucleosis and has been associated with Burkitt's lymphoma and nasopharyngeal carcinoma. The virus is an antigenically distinct herpesvirus.
Properties of the Virus. Morphology: EB virus is indistinguishable in size and structure from other herpesviruses.
Antigenic Properties: EB virus is distinct from all other human herpesviruses. Many different EB virus antigens can be detected by CF, immunodiffusion, or immunofluorescence tests. A lymphocyte-detected membrane antigen (LYDMA) is the earliest-detected virus-determined antigen. EBNA is a complement-fixing nuclear antigen. Early antigen (EA) is formed in the presence of DNA inhibitors and membrane antigen (MA), the neutralizing antigen, is a cell surface antigen. The virus capsid antigen (VCA) is a late antigen representing virions and structural antigen.
Angina in patient with infectious mononucleosis
Human Herpesvirus 6 and 7
Pathogenesis. The reservoir and mode of transmission of human herpesvirus 6 and 7 are not well understood at the present time. It should be noted that high prevalence of antibodies early in life would implicate transmission within the home from oropharyngeal secretions; however, this has not yet been documented.
Epidemiology. The epidemiology of human herpesvirus 6 and 7 is poorly understood at present. Loss of transplacental antibodies, followed by acquisition of antibodies early in life, implies horizontal transmission within the home environment. By the age of 5, antibodies are present in virtually 100 per cent of the population to both of these viruses. Human herpesvirus 6 exists as type A and B. The type A variant was the original isolate being retrieved from an immunocompromised host. The type B variant is associated with roseola. Some investigators suggest that the genetic differences in these two types warrant distinct names; thus, it is conceivable that the International Herpesvirus Nomenclature Committee may designate these agents as distinct.
Human Herpesvirus 6
Clinical Manifestations. Human herpesvirus 6, 7, 8 have recently been isolated. Human herpes virus 6 (as has human herpes virus 7, but to a lesser extent), has been associated with exanthem subitum, or roseola. This illness is characterized by 3 - 5 days of fever, followed by the appearance of a maculopapular "slapped cheek" rash. In addition, there has been an association between human herpesvirus 6 and rejection of transplanted kidneys, fulminant hepatitis and infections of the central nervous system.
Kaposi's Sarcoma Herpesvirus (HHV-8). Recently, a new herpesvirus has been associated with Kaposi's sarcoma and AIDS-related lymphomas of organ cavities. The DNA of this virus is partially homologous to the DNA of Epstein-Barr virus and that of herpesvirus saimiri. This virus immortalizes B lymphocytes. Isolation of the virus has yet to be achieved.