Viral infection

1. Viral infections

2. Viruses
 Obligate intra cellular parasites that
depend on hosts cell’s metabolic
machinery for their replication
 Has a nucleic acid genome surrounded
by a protein coat called capsid
 Sometimes encased in a lipid membrane –
envelope
 20-300nm in size
 Best visualized with electron microscope

4. Classification
 According to
 Nuclear genome
 Shape of capsid
 Presence or absence of lipid membrane
 Preferred cell type for replication
 Type of pathology
 Duration of infection

5.  DNA viruses
 Herpes
(HSV,CMV,EBV)
 Hepadna (hepatitis B)
 Adeno virus
 Pox (Vaccinia)
 Papova (papilloma)
 RNA viruses
 Orthomyxoviruses
(influenza A&B)
 Paramyxoviruses
(RSV,Mumps,
measles)
 Rota viruses
 Norwalk viruses
 Hepatitis A,C,E
 Retro viruses

6.  Shape of capsid
Icosahedral – all human DNA viruses
except pox virus
Helical – most of RNA viruses
 Lipid membrane
Enveloped – herpes, pox, hepadna, retro,
orthomyxoviruses, paramyxoviruses
Non enveloped – adeno , papova,
picorna, calcivirideae

11.  Respiratory system
 Rhino viruses – URTI
 Adenovirus - URTI,LRTI
 Influenza virus A&B – influenza
 RSV – bronchiolitis, pneumonia
 Coxsackievirus - SARS

12.  Digestive system
 Mumps virus – mumps, orchitis,
pancreatitis
 Rota virus - childhood diarrhoea
 Norwalk – gastroenteritis
 Hepatitis A,B,C,D,E – viral hepatitis

13.  Systemic with skin eruptions
 Measles virus – measles (rubeola)
 Rubella virus – German measles
 Parvo virus – erythema infectiosum
 Vaccinia virus – small pox
 Varicella-zoster virus – chicken pox,
shingles
 HSV – 1 – cold sore
 HSV – 2 – genital herpes

14.  Systemic with hematological
diseases
 Cytomegalovirus – cytomegalic
inclusion diseases
 Epstein-Barr virus – infectious
mononucleosis
 HTLV – 1 – adult T cell leukemia
 HIV-1 & HIV-2 - AIDS

15.  Arboviral & hemorrhagic fevers
 Dengue virus – dengue, hemorrhagic fever
 Yellow fever virus – yellow fever
 Regional hemorrhagic fever viruses
 Warty growths
 Papilloma virus – condyloma, cervical
carcinoma
 Central nervous system
 Polio virus – poliomyelitis
 JC virus – progressive mutifocal
leukoencephalopathy

16. Transient infections – some
viruses causes transient illness & are
eliminated from body
 Measles
 Mumps
 Poliovirus
 Viral hemorrhagic fever

17.  Chronic productive infections –
some viruses are not eliminated but
persist with in cells of host & continue
to multiply
 Hepatitis B

18. Chronic latent infection –some
viruses are not eliminated but persist in
host cells in non replicative form
 HSV
 CMV
 Varicella -zoster

19. Transforming – some viruses can
transform a host cell into tumour cell
 EBV
 HPV

20.  Different viruses can produce same
clinical picture
 Eg: URTI
 A single virus can cause different
clinical manifestations depending on
host age or immune status
 Eg: CMV

21. Mechanism of viral injury
 Viruses can directly damage host cell by
entering them & replicating in host’s
expense
 Tropism – prediliction for viruses to infect
certain cells and not others

22.  Determining factors of tropism
 Host cell receptor for virus
 Cellular transcription factors that
recognize viral enhancer & promoter
sequences
 Anatomic barriers
 Local temperature, pH, host defenses

23.  Major determinant is the presence of
viral receptor on host cell
 Viruses possess specific cell surface
proteins that bind to particular host
cell surface proteins

24.  Many viruses use normal cellular
receptors of host to enter the cell
 HIV gp 20 binds to
 CD4 on T cell
 Chemokine receptor CXCR4 on T cell &
CCR5 on macro phage
 Rhino virus bind to ICAM 1
( where LFA 1 , an integrin on surface
of lymphocyte which is important for
adhesion & migration binds)

25.  In some cases host proteases are
needed to enable binding of virus to
host cell
A host protease cleaves & activate
Influenza virus hemagglutinin

26.  Ability of virus to replicate inside
some cell but not in others is related
to presence of cell type specific
transcription factors
 JC virus is restricted to oligodendroglia
in CNS
(promoter & enhancer DNA
sequences upstream from viral gene are
active in glial cell but not in neuron or
endothelial cells)

27. Physical barriers contribute to
tropism
Entero virus replicate in intestine as
they can resist inactivation by acid,
bile, & digestive enzymes

28. Other factors
Rhino virus replicate only in URT
because they survive optimally at
lower temperature of URT

29.  Determining factors of tropism
 Host cell receptor for virus
 Cellular transcription factors that
recognize viral enhancer & promoter
sequences
 Anatomic barriers
 Local temperature, pH, host defenses

30.  Once viruses are inside the host cell they
can kill cell &/ or cause tissue damage in a
number of ways
 Viruses may inhibit host cell DNA, RNA or
protein synthesis
 Polio virus inactivate cap – binding
protein essential for host cell m-RNA but
leaves translation of polio viral m-RNA
unaffected

31. Virus may lyse host cell
 Respiratory epithelial cells are killed by
Influenza virus replication
 Liver cells by yellow fever virus
 Neurons by polio &rabies viruses

32.  Viruses may manipulate programmed
cell death (apoptosis)
TAT & gp 120 of HIV
Adeno virus E1A

33.  Viral proteins on surface of host cells
-recognized by immune system - host
lymphocyte attack virus infected cell
a/c liver failure during hepatitis B
infection is accelerated by T cell
mediated destruction of infected
hepatocyte

34.  Virus may damage cells involved in host
anti microbial defense - secondary
infections
 Damage to respiratory epithelium lead
to pneumonia by Streptococcus
pneumoniae& Haemophilus influenzae
 HIV deplete CD4 Tcells lead to
opportunistic infections

35.  Viral killing of one cell may lead to
loss of other cells that depend on
them
 Denervation of motor neuron by polio
virus lead to atrophy &death of skeletal
muscle supplied by it

36.  Some viruses can cause cell
proliferation & transformation
resulting in cancer
 EBV, HBV, HPV or HTLV 1 infection

37. Inflammatory responses to
infection
 Cytopathic & cytoproliferative inflammation
 Usually produced by viruses
 Characterized by cell necrosis or cellular
proliferation usually with sparse
inflammatory cells

38. Viral inclusions
 Some viral particles aggregate with in
cells - inclusion bodies
 Inclusions seen with light microscope
- useful for diagnosis

39. Nuclear inclusions
CMV – large eosinophilic
Herpes – large with surrounding halo
Cytoplasmic inclusions
CMV – small basophilic
Small pox
Rabies – negri bodies
Molluscum contagiosm – molluscum

45.  Some viruses induce cells to fuse &
form multinucleated cells called
polykaryons
Eg: measles , herpes

46.  Focal cell damage in skin may cause
epithelial cell to become detached
forming blisters
Herpes virus

47.  Some virus can cause epithelial cell
to proliferate
Venereal warts by HPV
Umbilicated papule of molluscum
contagiosm

48.  Finally viruses can cause dysplastic
changes & contribute to development
of malignant neoplasms

50. Transient viral infections
 Viruses that cause transient infection are
structurally heterogeneous,
 But each elicits an effective immune
response that eliminates the virus
 And may or may not confer lifelong
protection

51.  Mumps virus has only one serotype & infects
people only once
 Influenza virus can repeatedly infect same
individual because of antigenic variation
 Immune response to some infections wanes
with time & same serotype infects repeatedly

52. Measles
 Leading cause of vaccine-preventable
death & illness worldwide
 Epidemics of measles –in unvaccinated
 Can produce severe disease -with
defect in CMI (HIV,leukemia)

53.  Single stranded RNA virus
 Paramyxovirus family
 There is only one strain of measles virus
 2 cell surface receptors
 CD 46 – a complement regulatory protein that
inactivate C3 convertases
 Expressed on all nucleated cells
 SLAM (signaling lymphocytic activation
molecule)- involved in T cell activation
 Expressed on cells of immune system
 Both receptors bind to viral hemagglutinin
protein

54.  Spread by respiratory droplets
 Initially multiplies with in upper respiratory
epithelial cells
 Then in lymphoid tissue with in
mononuclear cells
(lymphocytes,macrophages &dentritic
cells)
 Then by blood through out the body

55.  Most children develop T cell mediated
immunity to measles virus that
 Controls viral infection
 Produce measles rash, a hyper sensitivity
reaction to virus
 Rash does not occur in patients with
deficient cell mediated immunity
 Does occur in agamaglobulinemia patients
 Antibody mediated immunity to measles
virus protects against re infection

56.  Measles may cause
 Croup
 Pneumonia
 Diarrhea with protein losing enteropathy
 Keratitis with scarring & blindness
 Encephalitis
 Hemorrhagic rashes
 Measles can cause immuno suppression

57.  Complications
Subacute sclerosing
panencephalitis
Measles inclusion body encephalitis

58.  Blotchy reddish brown rash is
produced by
Dilated skin vessels, edema &
moderate nonspecific mononuclear
perivascular infiltrate
 Koplik spots (ulcerated mucosal
lesions in oral cavity)
Marked by necrosis, neutrophilic
exudate & neovascularization

59.  Lymphoid organs have
Follicular hyperplasia
Large germinal centers
Warthin- Finkeldey cells –
randomly distributed multinucleated
giant cells which have eosinophilic
nuclear & cytoplasmic inclusion
bodies

61.  Milder measles pneumonia
Peribronchial & interstitial
mononuclear infiltrate
In severe /neglected – bacterial
superinfection

63. Mumps
 Member of paramyxovirus family
 Single stranded RNA
 Has 2 types surface glycoprotein
 One with hemagglutinin & neuraminidase
activity
 Other with cell fusion &hemolytic activity
 Enter upper respiratory tract through
inhalation of droplets

64.  Spread to lymph nodes & replicate in
lymphocyte
 Through blood to salivary & other
glands, infect ductal epithelial cells
 Resulting in desquamation of cells,
edema& inflammation
 Also can spread to – CNS, testes,
ovary & pancreas

65. Complications
Aseptic meningitis is the most
common extra salivary gland
complication
Occurring in 10 % cases

66. Morphology
 Mumps parotitis
 Bilateral in 70%
 Affected gland is enlarged & have a
doughy consistency
 On cross section moist glistening
&reddish brown
 On microscopy interstitium edematous&
diffusely infiltrated by macrophages,
lymphocytes& plasma cells which
compress acini & ducts

67.  Mumps orchitis
 Testicular swelling may be marked
 Caused by edema mononuclear cell
infiltration& focal hemorrhages
 since testis is tightly contained within
tunica albuginea, may compromise
blood supply leading to infarction
 Sterility when it occur is caused by scars
& atrophy of testis after resolution of
viral infection

68.  In pancreas
 Lesion may be destructive since
enzyme- rich
 Parenchymal & fat necrosis and
neutrophil rich inflammation
 Mumps encephalitis
 Causes perivenous demyelination &
perivascular mononuclear cuffing

69. Polio virus
 Spherical unencapsulated RNA
virus of enterovirus genus
 3 major strains of polio virus
 Each of 3 strains included in
 Salk formalin fixed vaccine
 Sabin oral attenuated vaccine
 Still present in India & Africa

70.  These vaccines may get rid of polio
from earth because
 Polio virus ( like small pox virus) infect
man but not other animals
 It is only briefly shed
 Does not under go antegenic variation
 It is effectively prevented by
immunization

71.  Transmitted by fecal – oral route
 First infect oropharynx & is secreted
to saliva & swallowed
 Then multiplies in intestinal mucosa
& CNS causing transient viremia &
fever
 Mostly asymptomatic

72.  In 1/100 persons polio virus invades CNS
& replicate in motor neurons of spinal cord
or brain stem
 Virus spread to nervous system may be
secondary to viremia or by retro grade
trans port of along axon of motor neuron

73.  The species specificity of polio virus
humans is determined by particular
amino acid residues that are present
in human receptor CD 155 – an Ig
super family member

74.  Rare cases of polio myelitis that occur
after vaccination are caused by
mutation of attenuated viruses to wild
type forms

75.  Morphology
 Ventral horns& base of dorsal horns are
infiltrated by lymphocytes & hypertrophied
microglial cells
 Neuronophagic nodules with neutrophils are
seen in early stages
 Meninges show inflammatory cell infiltration
 Earliest change in neurons is loss of Nissl
substance in cytoplasm
 Later eosinophilic necrosis & intranuclear
inclusions seen

76.  Long after onset of paralysis
 Loss of neurons in ventral horns
 Axon show wallerian degeneration
 Muscles show denervation atrophy

77. Viral hemorrhagic fevers
 Systemic infections characterized by fever
& hemorrhage
 Caused by enveloped RNA viruses in 4
different families – arena viruses,
filoviruses, bunya viruses& flavi viruses
 All depend upon animal or insect host
for survival & transmission VHF viruses
are restricted geographically to areas
where host resides

78.  Humans are infected when come into
contact with infected hosts or insect
vectors
 Humans are not natural reservoir for any
of these viruses
 Produce a spectrum of diseases ranging
from mild a/c disease characterized by
fever, myalgia, head ache rash,
neutropenia &thrombocytopenia to severe
life threatening disease with sudden
hemodynamic shock

79.  Pathogenesis not well understood
 Most VHF infect endothelial cells
 Hemorrhagic manifestations are due to
endothelial or platelet dysfunction or to
thrombocytopenia
 There is increased vascular permeability
 Necrosis & hemorrhage in many organ
often wide spread hepatocellular necrosis

80. Chronic latent infections
 HERPES VIRAL INFECTION
 Encapsulated viruses
 Double stranded DNA genome
 Causes infections followed by latent
infections in which viruses persist in non
infectious form with periodic reactivation
&shedding of viruses
 9 type of human herpes viruses belonging to
3 sub groups

81.  Alpha group
 HSV-1
 HSV -2
 Varicella – zoster
 These infect epithelial cells & produce latent
infection in neurons
 Beta group
 CMV
 Human herpes virus 6 – causes exanthem subitum &
6th disease
 HHV -7
 Infect & produce latent infection in variety of cells

82.  Gamma group
 EBV
 HHV -8 ; causes Kaposi sarcoma
 Produces latent infections mainly in
lymphoid tissue

83. Herpes simplex viruses
 Lesions include
 Self limited cold sores, gingivostomatitis &
corneal blindness (HSV-1)
 Genital sores (HSV -2)
 Life threatening disseminated visceral
infections& encephalitis
 In primary infections HSV replicate in skin
&mucus membrane (at site of viral entry )
causing vesicular lesions

84.  During reactivation, HSV residing latent
in neurons, spreads from regional ganglia
back to skin or mucus membrane
 HSV lesions show large pink purple virion
containing intra nuclear inclusions
(Cowdry type A inclusions),
compressing host chromatin against
nuclear membrane
 Also produce inclusion bearing
multinucleated syncytia (seen in Tzanck
preparation of fluid from blisters)

85.  Herpes stromal keratitis
 Mononuclear cell infiltrate around
keratinocyte &endothelial cells
 Neovascularisation, scarring,&
opasification of cornea
 Blindness
 Herpes epithelial keratitis
 With viral induced epithelial cytolysis

88. Cytomegalovirus
 In healthy children & adult
 Nearly always asymptomatic
 May manifest as mononucleosis like syndrome
 In neonates & immuno suppressed
 esophagitis
 Colitis
 Hepatitis
 Renal tubulitis
 Chorioretinitis
 Pneumonitis, deafness, brain damage
 thrombocytopenia

89.  Infection spread by
 Intra uterine & perinatal transmission
 In mother’s milk
 Respiratory droplets
 Saliva
 Semen & vaginal fluid
 In blood transfusion
 Infected transplanting grafts

90.  95%congenital infections asymptomatic
 CMV can produce cytomegalic inclusion
disease in infants esp if initial maternal
infection occur during pregnancy
 CID manifest by hemolytic anemia,
jaundice, hepatosplenomegaly,
pneumonitis, deafness, chorioretinitis,
brain damage& thrombocytopenia

91.  CMV is most common
opportunistic infection in AIDS
 Disseminated CMV in immuno
compromised hosts is life threatening
 Lungs, GIT& retina are affected with
focal necrosis & minimal inflammation

92.  CMV infection causes marked
cellular enlargement
 Characteristic large purple intra
nuclear inclusions surrounded by a
clear halo
 Smaller basophilic cytoplasmic
inclusions

94. Varicella – zoster virus
 A/c VZV infection causes chickenpox
 Reactivation of latent VZV causes
shingles (or herpes zoster)
 VZV infects mucous membranes, skin &
neurons establishing a latent infection in
sensory ganglia
 VZV transmitted by aerosols
 Disseminates hematogenously& causes
vesicular skin lesions

95.  Each skin lesion evolves rapidly from
macule to vesicles – dew drop
 Histologically vesicles contain epithelial
cell intra nuclear inclusions& blisters
identical to HSV
 Shingles occurs when latent VZV in dorsal
root ganglia reactivates, infecting sensory
nerves that carry viruses to skin
 Causes painful vesicular leision typically in
a dermatological distribution