36

Miscellaneous Viruses
RUBELLA VIRUS – GERMAN MEASLES yy BK virus can grow in a wide range of primary and continuous
cell cultures
yy Belongs to Togaviridae: Enveloped RNA virus
yy Infection is acquired from a clinical or subclinical case; no
carriers PARVOVIRIDAE
yy Gets transmitted by either droplet infection or vertical trans-
mission Parvo Virus B19 (Smallest Virus)
Sa

yy It will affect the children of 3–10 years yy Non enveloped ss DNA

yy Around 40% of the females are susceptible to infection; Hence
vaccination is must to avoid congenital syndrome
yy Depending upon the trimester – infection rate differs
m
yy Damage to fetus occurs most during first trimester
Congenital rubella syndrome: Cardiac defects, cataract and
deafness
pl
yy Smallest virus with smallest genome
yy Parvo virus B19 – causes infection in children
yy Parvoviruses has a special tropism for erythroid progenitor
cells in the adult bone marrow and fetal liver
yy It binds to the P antigen in the blood cell surface
yy Infection is acquired through respiratory route
yy It causes Slapped cheek disease or fifth disease or erythema

Expanded rubella syndrome – includes hepatosplenomegaly, infectiosum in children

thrombocytopenic purpura, myocarditis and bone lesions yy Causes aplastic crisis in children with sickle cell anemia
yy In adults it can cause arthropathy and aplastic anemia.
eC

Diagnosis yy In pregnancy, it leads to nonimmune fetal hydrops

IgM antibody: Acute infection; IgG means that person is immune
to Rubella infection
yy Vaccine strain: RA 27/3
yy MMR vaccine: Those who are vaccinated should avoid getting
pregnant for three months
ha

PAPOVAVIRIDAE
HUMAN PAPILLOMA VIRUS
pt

yy Belongs to Papovaviridae
yy Small, nonenveloped, DNA tumor viruses
er

Table 1:  HPV types and clinical illness

HPV 6, 11 Intraepithelial neoplasia
HPV 16, 18 Cervical cancer
HPV 1, 2, 3, 4 Verruca vulgaris
HPV 6, 11 Condyloma acuminatum Figure 1: Slapped cheek appearance caused by Parvo virus B19
yy Recombinant vaccine: (Courtesy: CDC)
 Bivalent vaccine: HPV 16, 18
Disease conditions associated with parvovirus:
 Quadrivalent vaccine: Gardesil – HPV 6, 11, 16, 18
•• Erythema infectiosum or fifth disease or slapped cheek
 Nonavelent vaccine: HPV 6, 11, 16, 18, 31, 33, 45, 52
disease in children
yy Vaccine is to be given for female population aged 9 to 26 years
•• Arthralgia or Polyarthropathy in adults
•• Transient aplastic crisis
POLYOMAVIRUS •• Pure red cell aplasia
yy JC virus – grows only in human fetal glial cell cultures •• Hydrops fetalis
yy BK virus – isolated in kidney transplant patients -nephropathy •• Papular purpura
 yy Human rotavirus does not grow in cell cultures, except Group
REOVIRIDAE

Chapter 36     Miscellaneous Viruses

A few strains have been made change to grow in serial culture.
ROTAVIRUS
yy Member of Reoviridae
Prophylaxis
yy Has 11 segments of dsRNA – characteristic feature is genetic yy Vaccine: Rotarix and Rotateq
reassortment yy Both are oral live attenuated vaccines
yy Vaccines should be given before 32 weeks of age – to avoid
intussusception
Rotarix (2 doses) P1 A (8) G 1
Rotateq (3 doses) G1, G2, G3, G4 and P (8)

Table 2:  Other gastroenteritis viruses

Virus Characteristics
Norwalk virus •• Family - calciviridae
••
Sa
Causes epidemics
•• Associated with consumption of raw oysters
•• Causes Adult diarrhea
Adenovirus •• Types 40, 41 causes diarrhea
m
Figure 2: Electron microscopic appearance of rotavirus •• Difficult to grow in culture
(Courtesy: CDC/ Dr. Erskine Palmer)
Astrovirus •• Star-shaped virus
yy Double walled viruses – Cart-wheel appearance •• Epidemics of diarrhea in children
yy Most common cause of diarrheal disease in infants and
pl

children Coronavirus •• Virus isolated in human feces

yy Rotaviruses can be classified into five species Group A to E •• Association with diarrhea unknown
based on the antigenic structural protein called VP6.
eC

yy Major antigens are VP6, VP4 and VP7 SLOW VIRAL DISEASE
yy Group A affects children
yy Some diseases in humans take slow or chronic persistent type
yy Group B – Adult diarrhea rotavirus (ADRV)
of infections called as slow viral diseases.
yy It also causes – SIDS, intussusception, necrotizing enterocolitis
yy They usually affect the central nervous system
and DM.

Characteristics
ha

Pathogenesis and Clinical Findings

yy Long incubation period
yy Rotaviruses infect the cells in the villi of small intestine
yy Course of illness last for months to years
yy Destruction of enterocytes leading to loss of villi and diarrhea
yy Involves CNS
yy Secretion of Enterotoxin – NSP4 (a viral encoded protein) –
pt
yy Absence of immune response
leads to triggering of signal transduction pathway
yy Genetic predisposition
yy This leads to activation of enteric nervous system
yy Invariable fatal termination
yy Diarrhea caused by rotaviruses are due to impaired sodium
er
and glucose absorption
yy It will take 3–8 weeks for restoration into normal villi. Classification
yy Incubation period is 1–3 days
yy Symptoms seen are watery diarrhea, fever, abdominal pain Table 3:  Classification of slow viral diseases
and vomiting.
Group A Lenti viruses - HIV
Group A rota viruses – most common cause of diarrhea in
Group B Prions
children
Group B viruses - causes diarrhea in adults Group C Subacute sclerosing polioencephalitis (SSPE
Progressive multifocal leucoencephalopathy (PML)

Laboratory Diagnosis
Group A
yy Direct detection of viral particles in stool by electron
yy Two animal viruses namely Visna and Maedi viruses are the
microscopy
agents that causes slow infections
yy IgM and IgG ELISA (Most common method employed)
yy Lentiviruses like HIV usually take up to 10 year’s time for
yy Most sensitive method – RT PCR
developing disease complex named AIDS
281
 Group B-Prions yy Three distint strains:
Unit 3     Virology

yy Prions are proteinaceous infectious materials

Zaire CFR 90%
yy They do not have DNA/RNA
yy The normal prion protein is PrPc gets converted to abnormal Sudan CFR 50%
prion protein - PrPsc and causes diseases Reston
yy Prions are highly resistant to routine sterilization methods
yy It can be disinfected only by: yy Recent outbreak – West Africa – 2013 to 2016
 90% phenol
yy Vaccine: rVSV – ZEBOV
 2 N NaOH
 10% Sodium dodecyl sulfate
 Autoclaving at 121°C for 1 hour

Prion Diseases
yy Subacute spongiform viral encephalopathies (Sequel to
measles virus)
yy Creutzfeldt Jakob disease
Sa
yy Kuru
yy SSPE
yy Progressive multifocal leukoencephalopathy

Basic Features for Prion Diseases Are

m

yy Neurodegeneration and spongiform changes Figure 3: Filamentous Ebola virus

yy Amyloid plaques are seen (Courtesy: CDC/ Frederick A. Murphy)
yy As the agents are not considered antigenic – the host do not
pl

mount immune or inflammatory response CORONA VIRUS

yy Prions are excreted in urine. yy Enveloped RNA viruses
yy Two groups:
Human Spongiform Encephalopathies
eC
 Acid labile viruses – causes cold

yy Two main encephalopathies associated with prions are  Acid stable viruses – causes gastroenteritis

 Kuru yy Types of corona virus:

 Classic Cueutzfeldt- Jakob disease (CJD)  229E

yy Kuru is not seen nowadays. It is spreaded once by old custom  OC43

among tribals by eating dead relatives (Cannibalism)  SARS – CoV

ha
yy CJD is developed because of transformation of normal prion  NL63 – New Haven corona virus

to abnormal prion proteins  HKU 1

yy CJD is manifested by progressive dementia, ataxia, myoclonus  MERS – CoV – previously named as novel coronal virus 2012

and death is usually seen within 6 months to 1 year
yy Two variants of CJD are:
 Gerstmann-Straussler-Scheinker (GSS) syndrome
 Fatal familial insomnia
yy CJD can also be transmitted through organ transplantation.
yy Severe acute respiratory syndrome (SARS) – spreads by
inhalation of the virus
pt
yy Virus undergoes high degree of mutation, vaccine is impossible
yy MERS-CoV – Middle east respiratory syndrome corona
virus – first detected in Saudi Arabia in 2012; It causes
er

Blood there is no proof for blood transfusion. severe respiratory illness; Epidemics occurs; No vaccine till
now; Severe cases can go for acute renal failure.

VIRAL HEMORRHAGIC VIRUS ONCOGENIC VIRUSES

Arenavirus Causes south American hemorrhagic fever Retrovirus
Lassa fever (transmitted through rodents) Human papilloma virus
Filoviruses Marburg and Ebola virus belongs to this group Polyoma virus
BK and JC virus
EBOLA VIRUS Molluscum contagiosum
Adenovirus
yy Named Ebola virus: after Ebola river, where the first cases
EBV
were noticed
yy Mode of infection: person to person transmission through HSV 1 and 2
blood and body fluids CMV
282
yy Causes fever with hemorrhagic illnes – highly fatal HBV and HCV
 MULTIPLE CHOICE QUESTIONS
1. Parvo virus B19 has predilection for: 
 (Recent Pattern 2018)
a. Erythroid progenitor cells
b. Myeloid progenitor cells
c. Haematopoietic stem cells
d. Lymphoid progenitor cells
2. Which HPV types causes Condyloma acuminata?
 (AIIMS Nov 2016)
a. 1 and 4 b. 6 and 11
c. 16 and 18 d. 31 and 33
3. Human papilloma virus is associated with all of the
cancers except: (AIIMS May 2015)
a. Cancer base of tongue
b. Tonsillar carcinoma
Sa
c. Nasopharyngeal cancer
d. Recurrent respiratory papilloma
4. Oropharyngeal cancer is associated with: (AIPG 2014)
a. EBV b. HPV
c. HSV d. HBV
m
5. Quadrivalent vaccine for HPV has all except: a. Belongs to family papovaviridae
 (PGI May 2013)
a. Type 7 b. Type 11
pl
c. Type 16 d. Type 18
e. Type 26
6. Slapped cheek appearance is seen in: (PGI May 2016)
a. Rubella b. Rubeola
eC
c. Parvo virus B19 d. HSV – 6
7. Parvovirus infection is associated with: 
 (PGI June 2008) (AIIMS May 2008)
a. Hydrops fetalis b. Aplastic anemia
c. Abortion d. Sixth disease
e. Hemophagocytic syndrome
ha
8. All are true about SARS except: (Recent Pattern 2012)
a. Epidemic in India b. Spreads by droplet
c. Diagnosed by PCR d. Caused by SARS CoV
9. SARS is a type of: (Recent Pattern 2014)
a. Corona virus b. Lenti virus
c. Calci viridae d. Hepadna viridae
10. Prions are: (AIPG 2004)
a. Infectious proteins b. Made up of virus particles
c. It is a nuclear material d. Can be cultured
11. Prions consists of: (AIIMS 2007)
a. DNA and RNA
b. DNA, RNA and proteins
c. RNA only
d. Proteins only
12. Which of the following is not prion associated disease
 (AIIMS 2003)
a. Scrapie b. Kuru
c. CJD d. Alzhiemers disease
13. True about prion diseases are all, except: (AIIMS 2010)
a. Myoclonus is seen in 10% of the patients
b. Caused by infectious protein
c. Brain biopsy is diagnostic
d. Manifests commonly as dementia
Chapter 36     Miscellaneous Viruses
14. True about prions: (AIIMS 2008)
a. Virus coded
b. Causes misfolding of proteins
c. Cleaves proteins
d. Defect in synthesis of proteins
15. Rota virus is detected by: (AIIMS 2002)
a. Antigen in stool
b. Antibody in serum
c. Demonstration of virus
d. Stool culture
16. Vaccination causing intussuception: (PGI pattern 2017)
a. Rotavirus b. Parvovirus
c. IPV d. BCG
e. Measles
17. Genetic Reassortment is typically seen in:
 (AIIMS Nov 2010)
a. Herpes virus b. Hepadna virus
c. Rotavirus d. Astro virus
18. True about Human papilloma virus: (PGI May 2017)
b. DNA virus
c. RNA virus
d. Enveloped
e. Causes anal warts
19. All are true about Ebola virus infection except:
 (PGI May 2017)
a. Air droplet is most common mode of transmission
b. Haemorrhagic manifestation may occur
c. Thai forest type – most common species in epidemics
d. Presents as sudden onset of fever and sore throat
e. Case fatality rate may be high as 70%
20. True about Human papillomavirus (HPV):
 (PGI Nov 2017)
a. ssDNA containing virus
b. Icosahedral symmetry
c. HPV type 16 and 18 causes cervical cancer
pt
d. Recently nine valent vaccine passed phase 3 clinical
trial
e. 5 genera of HPV identified
21. True about Ebola virus: (PGI Nov 2017)
er
a. Flavivirus
b. Icosahedral symmetry
c. Predominantly found in Africa
d. Spreads by direct contact with the blood or body fluids
e. Currently there is no specific treatment for this disease
22. Non immune hydrops is caused by:  (CET 2018)
a. Parvovirus b. HPV
c. Ehrlichia d. Rubella virus
23. Laryngeal papilloma is caused by  (CET 2018)
a. HPV 6 and 11 b. HPV 16 and 18
c. HPV 31 and 32 d. HPV 6 and 18
283
 ANSWERS AND EXPLANATIONS
Unit 3     Virology

1. Ans.  (a) Erythroid progenitor cells •• Parvo virus infection is associated with
ƒƒ Erythema infectiosum or fifth disease or slapped
Ref: Ananthanarayan and Paniker’s Textbook of Microbiol-
cheek disease in children
ogy – 10th ed – Page 558
ƒƒ Arthralgia or Polyarthropathy in adults
•• Parvo virus B19 causes Erythema infectiosum ƒƒ Transient aplastic crisis
•• Most common route is respiratory ƒƒ Pure red cell aplasia
•• It infects the precursors of RBC’s ƒƒ Hydrops fetalis
•• In children it causes rashes on the cheeks giving an ƒƒ Papular purpura
appearance of slapped cheek – hence called as slapped
cheek disease ; other wise called as fifth disease 8. Ans.  (a) Epidemic in India
•• It also causes transient aplastic crisis
Ref: Ananthanarayan and Paniker’s Textbook of Microbiol-
2. Ans.  (b) 6 and 11 ogy – 10th ed – Page
•• First time the outbreak of SARS happened in China in
Ref: Ananthanarayan and Paniker’s Textbook of Microbiol-
Sa
2002
ogy – 10th ed – Page
•• India escaped at that time
•• HPV types 6, 11, 40, 42 have very low oncogenic potential
•• They are the causes for benign conditions 9. Ans.  (a) Corona virus
•• Eg: Anogenital condylomas, larngeal papilloma,
Ref: Ananthanarayan and Paniker’s Textbook of Microbiol-
m

dysplasia and intraepithelial neoplasia

ogy – 10th ed – Page
3. Ans.  (c) Nasopharyngeal cancer •• SARS is a type of corona virus
pl
Ref: Ananthanarayan and Paniker’s Textbook of Microbiol- 10. Ans.  (a) Infectious proteins
ogy – 10th ed – Page
Ref: Jawetz medical microbiology – 27th ed – page 615
•• Nasopharygeal carcinoma is caused by EBV
•• Rest all others are associated with HPV •• Prions are infectious protein particles that does not have
eC

nucleic acid
4. Ans.  (b) HPV •• Prions are highly resistant
•• They have abnormal folding proteins – causes diseases
Ref: Harrisons T.B of medicine 18th ed, chapter 185
•• Most of the head and neck cancers are caused by HPV. 11. Ans.  (d) Proteins only
The most common head and neck cancer is oral cancer.
ha
Ref: Jawetz medical microbiology – 27th ed – page 615
5. Ans.  (a) Type 7, (e) Type 26 Ref: Q.10
Ref: Ananthanarayan and Paniker’s Textbook of Microbiol-
12. Ans.  (d) Alzhiemers disease
ogy – 10th ed – Page
pt

•• Bivalent vaccine – HPV 16, 18 Ref: Jawetz medical microbiology – 27th ed – page 615
•• Quadrivalent vaccine - Gardesil – HPV 6, 11, 16, 18 •• Prion causes the following diseases:
•• Nonavalent vaccine – HPV 6, 11, 16, 18, 31, 33, 45, 52 ƒƒ Kuru
er

ƒƒ CJD
6. Ans.  (c) Parvo virus B19 ƒƒ GSS
Ref: Ananthanarayan and Paniker’s Textbook of Microbiol- ƒƒ Fatal familial insomnia
ogy – 10th ed – Page ƒƒ Scrapie
ƒƒ Mad cow disease
•• In children, parvo virus causes rashes on the cheeks
ƒƒ Spongiform encephalopathy
giving an appearance of slapped cheek – hence called as
slapped cheek disease 13. Ans.  (a) Myoclonus is seen in 10% of the patients
•• It is other wise called as fifth disease
Ref: Harrison T.B of internal medicine – 18th ed – Page 3554
7. Ans.  (a) Hydrops fetalis, (b) Aplastic anaemia, •• Most of the patients of CJD has myoclonus that occurs
(c) Abortion (e) Hemophagocytic syndrome on and off throughout the illness
Ref: Ananthanarayan and Paniker’s Textbook of Microbiol- •• Most common human prion disease is sporadic CJD
ogy – 10th ed – Page

284

14. Ans.  (b) Causes misfolding of proteins
Ref: Harrison T.B of internal medicine – 18th ed – Page 3443
•• Prion is a infectious protein particle
•• The normal prion protein is PrPc gets converted to
abnormal prion protein - PrPsc and causes diseases
15. Ans.  (a) Antigen in stool
Ref: Harrison T.B of internal medicine – 18th ed – Page 1592
•• Diagnosis of rota virus is by:
ƒƒ Genotyping of viral nucleic acid – the most sensitive
method
ƒƒ Direct visualisation of fecal particles in electron
microscopy
ƒƒ Serological methods
ƒƒ They do not grow in cell culture except few strains of
group A
Sa
16. Ans.  (a) Rotavirus
Ref: Harrison T.B of internal medicine – 18th ed – Page 1592
•• First rotavirus vaccine was introduced in the year 1998
m
•• It was withdrawn then because of association with
intussuception
•• Then recently multivalent bovine human reassortment
pl
rotavirus vaccines were prepared
17. Ans.  (c) Rotavirus
eC
Ref: Harrison T.B of internal medicine – 18th ed – Page 1591
•• Genetic reassortment is characteristic of rota virus and
influenza virus
18. Ans.  (a) Belongs to family papovaviridae; (b) DNA
virus; (e) Causes anal warts
•• Already explained Q.2
ƒƒ Belongs to Papovaviridae
ƒƒ They are Small, nonenveloped, DNA tumor viruses
19. Ans.  (a) Air droplet is most common mode of transmis-
sion; (c) Thai forest type – most common species in ep-
idemics
Ref: Ananthanarayan and Paniker T.B of microbiology -
10th ed - page 562
•• It is named Ebola virus: after Ebola river, where the first
cases were noticed
•• Mode of infection: person to person transmission
Chapter 36     Miscellaneous Viruses
through blood and body fluids
•• Causes fever with hemorrhagic illnes – highly fatal.
20. Ans.  (a) ssDNA containing virus; (b) Icosahedral
symmetry; (c) HPV type 16 and 18 causes cervical
cancer; (d) Recently nine valent vaccine passed phase
3 clinical trial
Ref: Jawetz medical microbiology - 27th ed - page 631
•• HPV is a ssDNA virus with icosahedral symmetry
•• HPV 6,11 are benign
•• HPV 16,18 causes malignant illness - cervical cancer
•• Nonavalent vaccine is on use now
•• there are totally 16 genera and 82 types of HPV based on
genetic homology
21. Ans:   (c) Predominantly found in Africa; (d) Spreads
by direct contact with the blood or body fluids;
(e) Currently there is no specific treatment for this
disease
Ref: Ananthanarayan and Paniker T.B of microbiology -
10th ed - page 562
•• Ebola virus belongs to filoviridae; They are predom-
inantly seen in Africa and spreads person to person
through blood and body fluids; Currently there is no
specific management
•• Vaccines are under trail
22. Ans.  (a) Parvo virus
Ref: Ananthanarayan and Paniker’s Textbook of Micro­
biology – 10th ed – Page 558
•• Parvovirus causes:
ƒƒ Slapped cheek disease or fifth disease in children
ha
ƒƒ Non immune fetal hydrops in pregnancy
ƒƒ Aplastic anaemia in adults
23. Ans.  (a) HPV 6 and 11
pt
Ref: Jawetz medical microbiology - 27th ed - page 631
•• HPV 6 and 11 causes benign lesions – papillomas
•• HPV 16 and 18 causes malignant tumours
er
285
 HIGH YIELDING FACTS TO BE REMEMBERED IN VIROLOGY
Unit 3     Virology

Both intracytoplasmic and intranuclear inclusion bodies are Measles – Warthin-Finkeldey cells
seen in
DNA viruses Hepadna, Herpes, Adeno, Parvo, Papova, Pox
Segmented nucleic acid is seen in Bunya viridae, Orthomyxoviridae, Reoviridae, Arenaviridae
Smallest and largest DNA virus Parvovirus and Pox virus
Smallest and largest RNA virus Picornavirus and Paramyxovirus
Most commonly employed method for virus isolation Cell culture
Viruses causing hemagglutination Influenza, Measles, Rubella, Coxsackie, Rhinovirus, Rabies,
Parainfluenza, Toga, Entero, Echo, Reo
Microscopy of herpes lesions is by Tzanck smear – Giant multinucleated cells
What is Shingles? Reactivation of latent infections from the dorsal root ganglion – VZV –
Herpes zoster
Which is the reservoir of EBV Memory B cells
Sa

Malignancies associated with EBV Burkitt lymphoma, Hodgkin’s disease, T cell lymphoma, Nasopharyngeal
carcinoma
Most common viral organism causing intrauterine infection is Cytomegalovirus
Space vehicle shaped virus Adenovirus
m

Epidemic keratoconjunctivitis is caused by Adenovirus (Shipyard eye)

Condyloma acuminate is caused by which of the HPV HPV 6, 11
serotypes
pl

Erythema infectiosum is caused by Parvovirus – Slapped cheek disease or fifth disease

Outbreaks of vaccine-derived polio virus is due to OPV type 2
Hand foot mouth disease is caused by Coxsackie virus
eC

Acute hemorrhagic conjunctivitis is caused by Enterovirus 70

Unique feature of Influenza virus Antigenic drift and antigenic shift
Hecht’s pneumonia is caused by Measles
Most common cause of bronchiolitis Respiratory Syncytial Virus
Major vector for the transmission of KFD – Kyasanur Forest Ticks
ha

Disease
Earliest detection for Dengue virus illness is NS1 antigen detection
Only live vaccine that can be given during pregnancy when Yellow fever vaccine
needed
pt

Inclusion bodies seen in rabies and its location Negri bodies; most abundant in cerebellum and hippocampus
Vaccination schedule for rabies Day 0, 3, 7, 14, 28
er
Which group is called as adult diarrhea rotavirus? Group B virus
The most common cause of diarrhea in infant and children Rotavirus
Strains used in Rota teq and Rotarix G1, G2, G3, G4, P(8); G1 P (8)
Genetic reassortment is seen in Rota virus
The only DNA hepatitis virus is Hepatitis B virus
Enterically transmitted non A and non B hepatitis virus is Hepatitis E virus
Three types of particles in HBV Dane particles – complete hep B, Spherical particle which is the most
common, Filamentous or tubular particle
The first marker to appear in serum in HBV infection Hepatitis B surface antigen HBsAg
Qualitative and Quantitative marker for viral replication in HBeAg and HBV DNA
HBV
Most common cause of post-transfusion hepatitis and Hepatitis C virus
chronic hepatitis
286 Examples for defective viruses HDV and Adenoassociated viruses