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Permissive cells cells that support complete viral replication cycle yields infectious progeny virus causes cytocidal infection 2. Nonpermissive cells do not allow viral replication yield no infectious progeny virus causes abortive infection
T Y C P E S O F V V
1. CYTOCIDAL INFECTION associated with changes in cell morphology, physiology and biosynthetic events (many of these changes are necessary for efficient virus replication) leading to production of new infectious virus that kills the target cell PHYSIOLOGY EFFECT: may alter movement of ions, formation of secondary messengers, and activation cascades leading to altered
T T H E C E L L U L A R
1. Permissive 2 .
E L L
T Y P E S O F V I R A L I N F E C T I O N A I R A L I R L U E S V E P L R T OY PD EU C O T F I F OI A N NT F E E Ccellular activities O TF I HO ON S T C E L L
1. Cytocidal 2. Abortive
death
no effect
BIOCHEMICAL EFFECT: inhibit the synthesis of host cell DNA, RNA, and protein,
N .o n p e r m i s s i v 3 S e m i p e r m +s s i i S e m i p e r m i s s e +
s c e n
c e
3. Semipermissive cells may support some but not all steps of viral replication progeny virus may or may not be produced causes persistent infection
2. PERSISTENT INFECTION GENOTOXIC EFFECTS: breakage, fragmentation, rearrangement and/or changes in the number of chromosomes BIOLOGIC EFFECTS: alter host cell's antigenic or immune properties, shape, and growth characteristics
MECHANISMS OF VIRAL CYTOPATHOGENESIS
some viruses remain in specific cells for long periods of time without killing the infected cells TYPES: latent, chronic, and slow virus infections (the type of persistent infection usually influences the extent of cellular changes) LATENT PERSISTENT INFECTION - disease is produced, but the virus is not eradicated eg) latent HSV, VZV, adenovirus and some retroviral infections CHRONIC PERSISTENT INFECTION
MECHANISM
EXAMPLES
A lte ra tio n o f c e ll m e m b ra n e s tru c tu re Glycoprotein insertion Syncytia formation Disruption of cytoskeleton Permeability - All enveloped virus - H e r p e s s im p l e x v ir u s , V a r i c P al a a z o y t eo,rvHi rIiu u s , e l r m sx v Vs r - Nonenveloped virus, Herpes simplex virus - Togavirus, Herpesvirus
- cellular effects are similar to those of acute cytocidal infections, except that production of progeny may be limited to a few cells - eg) EBV, retroviruses
Formation of inclusion bodies Intracytoplasm ic Negri bodies Intranuclear Owls eye - Rabies - Cytomegalovirus
Intranuclear Cowdry type A - Herpes simplex virus, measles Intranuclear basophilic Intracytoplasmic acidophilic P e rin u c le a y to p la s m ic cr Toxicity of virion components - Adenovirus - Poxvirus - Reovirus
and Arenaviruses
Adenovirus fibers
SLOW PERSISTENT INFECTION - characterized by a prolonged incubation period, without significant morphological and physiological changes of infected cells
Mechanisms of Oncogenic Transformation 1. the tumor virus may introduce and express a so-called transforming gene in the cells, or 2. the tumor virus may alter the expression and/or coding capacity of preexisting cellular genes PATHOGENESIS
3. TRANSFORMING INFECTION DNA or RNA tumor viruses do not kill the cell, but produces genetic, biochemical, physiologic, and morphologic changes that may result in malignancy RNA tumor viruses transform cells to a malignant phenotype by integrating their own genetic material into the cellular genome and may also produce infectious progeny DNA tumor viruses transformation is associated with abortive infection Stages of Transformation 1. Immortalization - the cell gains the capacity for unlimited cell division 2. the immortalized cells acquire additional heritable genetic changes by which the cell is able to produce a tumor in an appropriate host
is the process by which an infection leads to disease Stages of viral disease 1. implantation of virus at the portal of entry 2. local replication and local spread 3. dissemination and multiplication into target organs (thru viremic or neural route) most common route of dissemination from the portal of entry is via the lymphatics. Virus may enter the target organs from the capillaries by: a) multiplying in endothelial cells or fixed macrophages b) diffusing through gaps c) being carried in a migrating leukocyte 1. spread to sites of shedding of virus into the environment
DISEASE
SITE OF
ROUTE
TARG ET ORGAN
SITE OF SHEDDING
R e s p ira t o r y t r a c t R e s p ira t o r y t r a c t
R e s p ira t o r y t r a c t R e s p ira t o r y t r a c t
Rotavirus
A lim e n ta r y t ra c t A lim e n ta ry t ra c t
Molluscum
P A T H O G E N E S& O F S E L E C T E S k in IR U Su IN FD IST IOM IN m T E o s a F E C T IO N D V & m c o s a C S k in & A u c D IN E SE N: S kin IS l S IT E O F IM P L A N T A T IO N Alim entary tract Alim entary tract In je c t io n , t r a u m a , in t e s t in e Alim entary tract Respiratory tract Respiratory tract Respiratory tract Respiratory tract Ganglion S u b c u ta n e o u s (b ite ) S u b c u ta n e o u s (b ite ) Penetration of skin Genital tract ROUTE OF SPREAD Blood Blood Blood Blood Blood Blood Blood CNS Liver TARG ET ORGAN SITE OF SHEDDING Alimentary tract Alimentary tract
DISEASE Poliomyelitis Hepatitis A AIDS Kuru Rubella Measles Chickenpox A cu te H S V ty p e 1 Recurrent HSV Rabies Arbovirus Hepatitis B HSV type 2
Skin , lung s, brain Respiratory tract Skin, lungs Respiratory tract, skin
N e r v e s , le u k o c y te s M a n y ( b r a in , liv e r , R e s p )ir a t o r y t r a c t , e p it h e lia s k in Nerves Nerves Blood Blood Nerves Skin, eye Brain Skin, eyes Salivary glands
Direct cell damage and death from viral infection may result from: PATHOGENESIS Factors that affect pathogenic mechanisms: 1. accessibility of virus to tissue 2. cell susceptibility to virus multiplication 3. virus susceptibility to host defenses Viral affinity for specific body tissues (tropism) is determined by: cell receptors for virus cell transcription factors that recognize viral promoters and enhancer sequences ability of the cell to support virus replication physical barriers local temperature, pH, and oxygen tension enzymes and non-specific factors in body secretions digestive enzymes and bile in the gastrointestinal tract that may inactivate some virus PATHOGENESIS
diversion of the cell's energy shutoff of cell macromolecular synthesis competition of viral mRNA for cellular ribosomes competition of viral promoters and transcriptional enhancers for cellular transcriptional factors such as VIRAL IMMUNOPATH RNA polymerases inhibition of the interferon defense mechanisms
IM M U NE
t h e h y p e r s e n s it iv it y a n d i n f la m m a t o r y r e a c t i o n s in it ia t e d b y a n t i v ir a l of the pathologic m anifestations and sym ptom s of viral disease IM M U N O P A T H O G E N E S I S Flu-like symptoms EXAMPLES
Indirect cell damage from viral infection can result from: M ED IATORS
interferon,
integration of the viral genome lymphokines induction of mutations in the host genome T cells, macrophages, Enveloped virus hypersensitivity and Inflammation inflammation host immune response
Delayed type PMN C la s s ic t y p e III im m u n e Antibody, complement c o m p le x h y p e r s e n s it iv it y reaction H em orrha gic dise ase T cell, antib od y, co m p lem ent T cell Dengue virus Hepatitis B virus, rubella
P o s tin fe c tiocy to ly s is n
Im m unosuppression
H IV , C M V , m e a s le s v ir u s , in f lu
VIRAL TRANSMISSION MODE Respiratory Fecal-oral Contact EXAMPLES - P a r a m y x o vI nrfu u e n z cao, r n a v iR u s n o v Ern tse, r o v, i VuZsV , P a r v o v i r u s ( B 1 9 ) , i ls Pi , rhi i u r - P ic o r n a v ir u s t a v iru s ,o v ir ,uC a lc ic iv ir u so r w a lk v ir u s , A d e n o v ir u s , Ro Re s , N - HSV, Rhinovirus, Poxvirus, Adenovirus
( le s io n s , s a liv a , f o m it e s ) Zoonoses (anim als, insects) Blood Sexual contact Transplacental Genetic - HIV, T-cell photropic lym virus-1, hepatitis B, C, D virus, CM V - H IV , T -c lyll p h o tro p ic s -1 , h e p a titis B , C , D v iru s , C M V , H S V , H P V em v iru - Rubella virus, CMV, Parvovirus, Echovirus, HSV, VZV Prions, Retrovirus - T o g a v i, rFula v iv i,rB u n y a v,iOur s i v i,rA rse n a v ,i rR a b i e s vO rruf(sp,o x ) v i r u s s us r b u us i
INCUBATION PERIOD DISEASE Chickenpox Mumps Mononucleosis Hepatitis A Hepatitis B Rabies Warts (HPV) AIDS (HIV) DAYS 12 14 13 17 16 20 30 50 15 40 50 150 30 100 50 150 1 10 years
G e r m a n m e a s le s ( r u b e 17) 20 lla