PAPOVAVIRUSES

PREPARED BY : FRANCIS SM MAKANYA

MMED-2 MICROBIOLOGY AND IMMUNOLOGY

FACILITATOR : DR. ABDALLAH BAJA

 OUTLINE
• INTRODUCTION TO PAPOVAVIRUSES
• CLASSIFICATION OF PAPOVAVIRUSES
• PROPERTIES OF PAPOVAVIRUSES
• VIRUS ISOLATION AND ANIMAL SUSCEPTIBILITY
• PATHOGENESIS AND IMMUNITY
• CLINICAL SYNDROMES
• EPIDEMIOLOGY
• LABORATORY DIAGNOSIS
• TREATMENT
INTRODUCTION TO PAPOVAVIRUSES
• The family Papovaviridae consists of papovaviruses, which are a group of viruses
containing small, enveloped, icosahedral capsid with a double-stranded, circular
DNA.
• The term papova is derived from the first two letters of the names of the viruses
(pa, papillomaviruses; po, polyomaviruses; and va, vacuolating agents).
• The family is divided into two genera as follows :
i) Papillomavirus
ii) Polyomavirus.

• Currently, the genus Papillomavirus is separated into a new family Papovaviridae,

and the genus Polyomavirus into a new family Polyomaviridae.
Cont..
• The papovaviruses encode proteins that promote cell growth.
• They induce both lytic infections and tumors (benign or malignant).
• These viruses are capable of causing lytic, chronic, latent, or
transforming infections depending on the host cells infected.
 Human Papillomaviruses
• Human papillomaviruses (HPVs) are the causative agents of
papillomas, which are the benign tumors of squamous cells or warts
on the skin.
• These are also associated with cancerous conditions in humans, such
as cervical carcinoma.
CLASSIFICATION OF HUMAN PAPILLOMAVIRUSES

• Based on DNA homology, tissue tropism, and association with

oncogenesis, the HPVs have been classified into 16 groups (A–P),
containing at least 70 types.
 PROPERTIES OF HUMAN
PAPILLOMAVIRUSES
1. Morphology
Human papillomaviruses show following features:
• They are double-stranded DNA virus without any envelope.
• The viruses are slightly larger than polyomaviruses and measure 50–55 nm diameter.
• They have an icosahedral capsid, composed of 72 capsomeres.
• The viral genome is a supercoiled, double-stranded DNA composed of approximately
3000 base pairs (bp).
• The DNA encodes seven to eight early genes (E1–E8) and two late (L1 and L2) genomes.
All these genes are present in a single strand, that is the “+” strand.
• Two of the early genes E6 and E7 are implicated in carcinogenesis, whereas E1 and E2
participate in DNA replication.
Cont..
2. Viral replication
• Papillomaviruses show tropism for epithelial cells of the skin and mucous membranes.
• The viruses during their replication in epithelial cells are dependent on the specific
factors that are present in sequential differentiated states of epithelial cells.
• The early genes of the virus are responsible for growth of cells and facilitate replication
of viral genome during cell division.
• The virus-induced cell growth causes thickening of the basal and prickle cell layer of
stratum spinosum.
• The late genes encode for the expression of structural proteins, which are present in
the differentiated upper layers of the skin.
• This causes the tissues to be excreted with the dead cells of the upper layer
Cont..
3. Antigenic and genomic properties
• The HPVs show a widespread diversity.
• Based on the homology between their genomes, more than 100 distinct
HPVs have been recognized.
• Certain HPV types show distinct predilection for infecting certain
tissues.
• Approximately 30 types of HPVs infect the genital tract: HPV-6 and
HPV-11 causing the genital warts.
• HPV types 1–6 primarily cause skin warts.
 VIRUS ISOLATION AND ANIMAL SUSCEPTIBILITY

• Human papilloma viruses do not grow on any cell culture.

• Hence, cell cultures are not useful for diagnosis of HPV infections.
 PATHOGENESIS AND IMMUNITY

• Human papilloma viruses show high degree of host specificity.

• They show a high predilection for the skin and also for mucous
membrane.
• HPV infection is acquired by close contact, and the infection is
initiated by infections of the skin or mucous membranes.
• Tissue tropism and manifestation of the disease depend on the HPV
type that causes disease.
Cont..
Pathogenesis of human papilloma virus infections
• After infection, the virus replicates in the squamous epithelium of the skin to
cause warts and in the mucous membrane to induce epithelial proliferation, such
as oral, genital, and conjunctival papillomas.
• The warts occur as a result of virus-caused cell growth and thickening of the basal
and prickle layers of the stratum spinosum as well as the stratum granulosum.
• The presence of the koilocytes is the hallmark of the HPV infections of the skin.
• These koilocytes are the enlarged keratocytes with well-demarcated halos
surrounding small nuclei.
• The HPV infection always causes a localized infection and the warts usually
resolve spontaneously possibly as a result of immune response.
Cont..
• Human papilloma virus has also been associated with development of
oral premalignant conditions as well as malignant conditions in
humans.
• HPV-16 as well as HPV-18, HPV-33, and HPV-35 have been linked
with:
(a) verruciform proliferation in the oral cavity
(b) oral premalignant lesions
(c) oral squamous cell carcinoma
Cont..
Host immunity
• The exact mechanism responsible for resolution of papillomas is not
known.
• Cell-mediated immunity, however, appears to play an important role in
the resolution of the disease.
• The conditions that depress cell-mediated immunity, such as in
patients with HIV and those receiving immunosuppressive therapy,
give rise to exacerbation of HPV infection and leads to more severe
manifestation of the disease.
 CLINICAL SYNDROMES
• Human papilloma virus infection causes:
(a) cutaneous warts
(b) benign head and neck tumors
(c) genital warts
(d) cancerous conditions in humans
Cont..
(a) Cutaneous warts
• Cutaneous warts are commonly caused by HPV-2, HPV-4, and HPV-7.
• Warts usually develop on the hands and feet after incubation period of
3–4 months depending on the HPV type and the site of infection.
• They may appear flat, plantar, or dome shaped.
• The plantar and flat warts are most common in children and young
adults.
• Wart is usually a benign and self-limiting condition, which resolves
during the course of time.
Cont..
(b) Benign tumors of head and neck
• These include oral papilloma, laryngeal papilloma, and conjunctival papilloma.
• Oral papillomas are usually single but may be multiple.
• They are sessile, verrucous, and white with raised borders.
• These lesions usually appear on the lips, hard palate, or gingiva.
• Focal epithelial hyperplasia or Heck disease is commonly caused by HPV-13 and HPV-32.
• This condition manifests as multiple, smooth, and sessile nodules present on the mucosal
surface of the lower lip or on the buccal mucosa.
• Laryngeal papillomas are life-threatening conditions in children, caused by HPV-6
and HPV-11.
• This is the most common benign epithelial tumor of the larynx.
Cont..
(c )Genital warts
• Genital warts or condyloma acuminata is caused by HPV-6 and HPV-
11.
• The condition typically manifests as solitary or multiple cerebriform
and pink lesions, which appear more commonly on the nonkeratinized
mucosa than on the keratinized mucosa.
• These genital lesions may also spread to the oral cavity during sexual
activity involving orogenital contact.
Cont..
(d)Cancerous conditions
• Certain types of HPV—commonly, HPV-16 and less frequently, HPV-18,
HPV-33, HPV-35—have been associated with oral premalignancy and
malignancies in humans.
• These conditions are associated with verruciform proliferations in the oral
cavity.
• Oral premalignant lesions and oral squamous cell carcinoma caused by HPV-
16 and HPV-18 are most commonly associated with intraepithelial cervical
neoplasia and cancer.
• The conditions progresses from mild to moderate neoplasia to severe dysplasia
or carcinoma in situ during a period of 1–4 years.
 EPIDEMIOLOGY
Geographical distribution
• HPV infections are found worldwide.
Cont..
Reservoir, source, and transmission of infection
• Human papilloma viruses have been detected in the oral cavity of
estimated 6–10% of children and adolescents, and in 5–80% in healthy
adults.
• HPVs are found in genital secretions and skin sheddings, which
contain virus.
• Infected humans are the main source of infection.
• Asymptomatic shedding of viruses in body secretions facilitates
transmission of infection to other human hosts.
Cont..
• The infections are transmitted primarily by skin-to-skin contact and by
genital contact. They are transmitted:
-most commonly by sexual contact (HPV-16, HPV-18);
-by direct contact through abrasions in the skin and mucosa;
-by passage through infected birth canal as for laryngeal papilloma
(types 6 and 11).
 LABORATORY DIAGNOSIS
• The diagnosis of wart is made by histopathological examination.
• Demonstration of hyperplasia of the prickle cells and excessive
production of keratin (hyperkeratosis) is diagnostic of the condition.
• Human papilloma virus infection can be detected by the demonstration of
round coalesced cytotic squamous epithelial cells occurring in clumps in
Papanicolaou smears.
• Cell cultures are not useful, because HPVs do not grow in cell lines.
• Serology is rarely used.
• The typing of virus isolates may be carried out by immunohistochemical
detection of HPV structural proteins.
 TREATMENT
• Warts are regressed during the course of time over a period of months
to years.
• The warts can be removed by surgical cryotherapy, electrocautery, or
chemical reagents.
 PREVENTION AND CONTROL
• No specific preventive measures are available against HPV infection.
• Avoidance of direct contact with infected warts may prevent
transmission.
• Safe sexual practice will be useful to prevent sexual transmission of
HPV.
 POLYOMAVIRUSES
• Simian virus 40 (SV40) is the prototype polyomavirus studied
extensively for eliciting different properties of the virus.
• The human polyomaviruses, such as BK and JC viruses, usually cause
asymptomatic infection in humans.
• Polyomaviruses (poly, many; oma, tumor) are smaller viruses than
papillomaviruses, measuring 45 nm in diameter.
• They are nonenveloped viruses with a 72-capsomere icosahedral
capsid.
Cont..
• Viral genome is a double-stranded DNA containing less nucleic acid,
approximately 5000 bp.
• The genomes of polyomaviruses (BK, JC, and SV40) are similar to each
other.
• The genome is divided into early, late, and noncoding regions.
• The early region codes for nonstructural transformation protein, while
the late region codes for three viral capsid proteins, such as VP1, VP2,
and VP3.
• The noncoding region contains the site of the origin of DNA for
replication.
Cont..
• Different polyomaviruses show different host specificities.
• Human polyomaviruses, such as JC and BK, probably enter through
the respiratory tract, and then subsequently infect lymphocytes and the
kidneys.
• The BK viruses cause latent infection of the kidney and of B cells. The
pathogenesis of the human polyomavirus infection in humans depends
on the immune status of the host.
• In the immunocompetent host, the replication of viruses is inhibited.
Cont..
• Suppression of immunity in patients receiving organ transplantation or
suffering from AIDS results in reactivation of latent JC and BK
viruses.
• In these patients, reactivation of viruses leads to shedding of viruses
and symptomatic infection.
• The reactivation of BK viruses causes severe urinary tract infection
with excretion of the virus in urine.
• Reactivation of JC viruses causes viremia and spread of the virus to
the central nervous system (CNS), causing infection of the CNS.
Cont..
• All the polyomaviruses (BK, JC, and SV40) are known to cause tumor in
animals, such as hamsters. These viruses, however, are not associated with
any tumors in humans.
• Primary infection by human polyomaviruses is mostly asymptomatic in
immunocompetent host.
• In immunocompromised host, the tissues are reactivated causing many
serious diseases
• Both JC and BK viruses are ubiquitous.
• Most people are infected by these two viruses by the age of 15 years.
• Both the viruses are probably transmitted by respiratory route.
Cont..
• BK virus is associated with haemorrhagic cystitis in the bone marrow
recipients. It also causes urethral stenosis in patients receiving kidney
transplant.
• JC virus was first isolated from the brain of a patient with Hodgkin’s
disease, who developed progressive multifocal leukoencephalopathy
(PML).
• PML is a subacute demyelinating disease of the CNS and is usually
fatal. This disease occurs usually in immunocompromised patients
including the patients with AIDS, Hodgkin’s disease, and chronic lym-
phocytic leukemia.
Cont..
• The SV40 shows oncogenic potential in new-born hamsters, but is not
associated with any human disease.
• The SV40, however, has a public health importance.
• Earlier, some batches of polio vaccines, which were prepared in the
simian cell culture were contaminated with undetected SV40 virus in
the primary monkey cell cultures.
• However, no SV40- related tumors have been reported so far, although
many people were vaccinated with these SV40 contaminated polio
vaccines.
 Laboratory Diagnosis
• Electron microscopy is useful to detect JC virus in brain tissue from
the cases of PML and from urine of kidney transplant recipients.
• Immunoperoxidase and in situ immunofluorescence are rapid
detection methods for detection of viral antigen in brain tissue
obtained by biopsy or at autopsy.
• BK polyomavirus is isolated from urine by culture in human diploid
fibroblasts; JC virus is isolated from urine and brain tissue by culture
in human fetal glial cell culture.
• Hemagglutination inhibition test is performed to differentiate these
two viruses .
 Treatment and Prevention
• No specific antiviral treatment is available for polyomavirus infections
in humans.
• Prevention of polyomavirus infection is difficult due to ubiquitous
presence of these viruses.
 REFERRENCES
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Immunology. 2ND Edition.
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Medical Microbiology. Publ. Mosby, USA.
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Microbiology and Microbial infections. Publ. Oxford University Press,
New York