Chapter 18

Chapter 18 

Eucaryotic Viruses and other 

acellular infectious agents 

11-25-2008 

11-26-2008 

1

Taxonomy of Eucaryotic Viruses 

• most of the ~5,000 known viruses infect 

eucaryotic organisms 

• Virus classification by the ICTV 

• Genome structure 

• Replication strategy 

• Morphology 

• Genetic relatedness 

Copyright © The 

McGraw-Hill 

Companies, Inc. 

Permission required 

for reproduction or 

display 2

Viruses that Infect Vertebrates 

Figure 18.1 


McGraw-Hill 




display 3

Reproduction of Animal Viruses 

• adsorption 

• penetration and uncoating 

• replication of virus nucleic acids 

• synthesis and assembly of virions 

• virion release 


McGraw-Hill 




display 4

Table 18.1 


McGraw-Hill 




display 5

Penetration and Uncoating 

• fusion of envelope with host cell 

membrane 

Fig 18.4 


McGraw-Hill 




display 6

Endocytosis – enveloped virus 

Figure 18.4 (b) 


McGraw-Hill 




display 7

Endocytosis – naked virus 

Figure 18.4 (c) 


McGraw-Hill 




display 8

Replication and transcription in DNA Viruses 

- Herpes simplex virus I 

uses host RNA 

polymerase for 

synthesis of viral 

mRNA 

uses virusencoded 

DNA 

polymerase for 

genome replication 



McGraw-Hill 




display 9

Poxviruses 

• large, morphologically complex doublestranded 

DNA (dsDNA) viruses 

• virion carries DNA-dependent RNA 

polymerase that synthesizes early 

mRNA 

• encodes DNA polymerase and other 

enzymes needed for DNA replication 


McGraw-Hill 




display 10

Hepadnaviruses- HBV 

• circular, partial dsDNA genome 

• transcribed by host RNAP 

• generates several mRNA molecules 

• one for pregenome RNA 

• others encode polymerase with reverse 

transcriptase activity 

• pregenome converted to dsDNA by virus polymerase 

(+RNA -DNA 2S DNA) 

11

Replication and Transcription 

in RNA Viruses 

• very diverse reproductive strategies 

• four general modes of replication and 

transcription 

12

Pico-RNA 

Para- and ortho- 

Myxo- affinity to mucin 

Respiratory-enteric-orphan 



McGraw-Hill 




display 13

Assembly of Virus Capsids 

• late genes direct capsid protein 

synthesis which spontaneously selfassemble 

to form the capsid 

• during icosahedral virus assembly 

empty procapsids form first, nucleic acid 

are then inserted 

• assembly of envelope viruses 

• in most cases, similar to assembly of 

naked viruses 


McGraw-Hill 




display 14 

• site of morphogenesis varies



McGraw-Hill 




display 15

Virion Release 

• naked viruses 

• usually by lysis of host cell 

• envelope viruses 

• formation of envelope and release usually 

occur concurrently (budding) 

• virus-encoded proteins incorporated into host 

membrane 

• nucleocapsid buds outward and is surrounded 

by modified host membrane 


McGraw-Hill 




display 16

Release of influenza virus by budding 



McGraw-Hill 




display 17

HIV release 

by budding 

Figure 18.12 (a) 


McGraw-Hill 




display 18

Mechanisms of host cell damage 

and cell death 

• inhibition of host DNA, RNA, and protein 

synthesis 

• lysosome damage 

• causes release of hydrolytic enzymes 

• alteration of plasma membrane 

• lead to attack of host by immune system 

• lead to cell fusion, forming syncytium 


McGraw-Hill 




display 19

Other mechanisms… 

• toxicity from high concentrations of viral 

proteins 

• formation of inclusion bodies 

• can disrupt cell structure 

• the Negri bodies in rabies infected neurons 

• chromosomal disruptions 

• transform host cell into malignancy 


McGraw-Hill 




display 20

Types of viral infections (Fig. 18.3) 

• acute infections 

• rapid onset and relatively short duration 

• persistent infections- last many years 

• Chronic infection, e.g, HBV infection 

• Latent infection, e.g., Herpes virus infection 

- 

21

Types of persistent infections 

• chronic virus infection 

• virus almost always detectable 

• clinical symptoms mild or absent for long 

periods 

• latent virus infection 

• virus stops reproducing and remains 

dormant for some time 

• during latency, symptoms, antivirusantibodies, 

and viruses are not detectable 


McGraw-Hill 




display 22

Possible causes of persistent 

infections 

• integration of viral genome into host 

genome 

• decrease in antigenicity of virus 

• mutation to less virulent and slower 

reproducing form 

• defective interfering (DI) particle – deletion 

mutant that cannot reproduce and slows 

reproduction of normal virus 


McGraw-Hill 




display 23

Slow virus diseases 

• Symptoms take years to emerge 

• subacute sclerosing panencephalitis caused 

by measles virus 

• HIV infections 

• Prion 


McGraw-Hill 




display 24

Prion 

• A small proteinaceous infectious 

particle 

• Passes through the filter (100 nm) 

and still transmits disease 

• resistant to a wide range of 

chemical and physical treatment 

• inactivated at 121 o C 1 h

Prion-caused degenerative diseases 

• Scrapie 

• bovine spongiform 

encephalopathy (BSE) or 

mad cow disease 

• Creutzfeldt-Jakob 

disease (CJD) and 

variant CJD (vCJD) 

• Kuru 

Scrapie- cause intense itching 

- The prototype of prion 

- A natural progressive brain disease 


McGraw-Hill 




display 26

Kuru- “shivering” or “ trembling” 

• 1950, occurred in the Fore 

tribe of New Guinea 

highlands 

• Related to the cannibalistic 

practices 

• Blurred speech, silly smiles, 

and dementia 

lose the ability to walk, talk, and see

The 1 st 

Nobel Prize for prion study 

• 1976, Carleton Gajdusek (1923~) 

• retired as chief of the laboratory of CNS at NIH 

• Demonstrated Kuru’s etiology 

• an infectious invisible slow 

(~ 30 y incubation period) virus as 

that of Scrapie? 

• Never saw any inflammation!

Creutzfeldt-Jakob disease (CJD) 

• The human form of mad cow disease 

• BSE (Bovine Spongiform encephalopathy) 

• Identified by Creutzfeldt and Jakob (1920) 

• A progressive fatal neurodegenerative 

disease 

• Usually aged between 50~75 

• Characterized by seizures, massive incoordination, 

dementia

Transmission of CJD 

• Injection with contaminated growth hormone 

• Transplantation of contaminated corneas 

• Contact with contaminated medical devices 

• brain electrodes- “Iatrogenic” 

• Ingestion of infected tissue 

• 1996 in UK, causes an unusual incidence of CJD in 

young people (

Inheritable CJD- prnp 

• A Gerstmann-Straussier-Scheinker syndrome 

• A Kuru like familial disease Inherited forms 

emerge earlier (~ 45 yr) 

• familial CJD, GSS, fatal familial insomnia (FFI)- 

10~15% 

• specific mutation of the gene on chromosome 20- 

prnp

Current Model 

of Disease Production by Prions 

• PrP C (prion protein): “normal” form 

• PrP Sc : abnormal form 

• entry of PrP Sc into animal brain causes 

PrP C to change its conformation to 

abnormal form 

• the newly produced PrP Sc convert more to 

the abnormal form 

• interactions between PrP Sc and PrP C 

crosslinking of PrP C neuron loss 


McGraw-Hill 




display 32

The 2 nd Nobel prize- 

Prion pathogenesis 

• PrP sc binds to the normal PrP c 

on the cell surface, causing it to 

be processed into PrP sc - a 

replicating protein, to be 

released from the cell, and to 

be aggregated as amyloid-like 

plaques in the brain 

• Vacuolated neurons (loss of 

function and lack of an immune 

response) 

• 1997, Stanley Prusiner 

(1942~) for showing that 

PrP sc is sufficient to 

cause disease 

• Director of institute of 

neurodegenerative disease 

UCSF

Viruses and Cancer 

• tumor 

• growth or lump of tissue 

• neoplasia 

• abnormal new cell growth and reproduction due to 

loss of regulation 

• anaplasia 

• reversion to a more primitive or less differentiated 

state 

• metastasis 


McGraw-Hill 




display 34 

• spread of cancerous cells throughout body

Carcinogenesis 

• complex, multistep process 

• often involves oncogenes 

• cancer-causing genes 

• many involved in regulation of cell growth and 

differentiation 

• some viruses contribute to carcinogenesis 


McGraw-Hill 




display 35

Viruses implicated in human 

cancers 

Epstein-Barr virus 

Hepatitis B virus 

Hepatitis C virus 

Burkitt’s lymphoma 

nasopharyngeal 

carcinoma 

liver cancer hepatoma 

liver cancer 

Human herpesvirus 8 

HIV 

human papillomavirus 

HTLV-1 and HTLV-2 

Kaposi’s sarcoma 

cervical cancer 


McGraw-Hill 



leukemia 


display 36

Possible mechanisms by which 

viruses cause cancer 

• carry oncogene into cell and insert it 

into host genome 

• altered cell regulation due to changes in 

kinase activity or production of 

regulatory proteins 

• insertion of promoter or enhancer next 

to cellular oncogene 


McGraw-Hill 




display 37

Chapter 37 

Human Diseases Caused by 

Viruses 

38

Airborne Diseases 

• when human is source, airborne viruses 

are propelled from respiratory tract by 

coughing, sneezing, or vocalizing 

39

Chickenpox (Varicella) 

• caused by varicella-zoster virus 

• results from initial infection 

• Attenuated vaccine 

40 

Figure 37.1

Shingles (herpes zoster) 

• postherpetic neuralgia 

• reactivated form of chickenpox 

Figure 37.2

Flu or common cold 

• clinical manifestations 

• chills, fever, headache, malaise, and general 

muscular aches and pains 

• recovery usually within 3 to 7 days 

• often leads to secondary infections by bacteria 

• rhinitis, tonsillitis, laryngitis, bronchitis, and 

pneumonia 

• treatment, prevention, and control 

• symptomatic/supportive therapy 

• inactivated virus vaccine 

42

43 

Influenza (Flu) by influenza virus 

• Orthomyxovirus (segmented virus) 

• Classified into A, B, and C groups 

• 16 HA and 9 NA 

• Influenza Pandemics 

• 1918, HswN1 (Spanish flu) 

• 50~ 100 million moratlity 

• 1947, H1N1 

• 1957, H2N2 (Asian flu) 

• 1968, H3N2 (Hong Kong flu) 

• 1977, H1N1 (Russian flu) 

• Avian flu- H5N1(1997~)

Generation of a reassortant virus 

- broad host range and segmented genome 

Reassortant virus

Avian flu virus 

• H9N2 (1998/1999) 

• China and Hong Kong 

• H7N7 (2003) 

• Netherlands 

• H5N1 in human 

(1997~2003~) 

• Hong Kong, China, and 

worldwide…. 

• since 2003, > 300 

infected and > 150 died 

Emerging Infectious Diseases (2007) October

SARS (Severe Acute Respiratory Syndrome) 

• An emerging disease cause by coronavirus 

• Flu-like syndrome 

• Vaccine target? 

- Virus of the year (2002-2003) 

Where is the SARS virus?? 

Box18.1 

- a mutation in spike protein 

46

Classification of coronaviruses 

• 3 groups coronaviruses: 

• groups 1 and 2: mammalian viruses 

• group 3 contains only avian viruses 

• Classified into distinct species by host 

range, antigenic relationships, and 

genomic organization 

47

Phylogenetic analyses of SARS-CoV sequences 

48

Measles (Rubeola) 

• caused by measles virus 

• subacute sclerosing 

panencephalitis 

• rare progressive degeneration of 

central nervous system caused 

by measles virus 

• treatment, prevention, and 

control 

• symptomatic/supportive therapy 

• attenuated measles vaccine 

• MMR vaccine (measles, 

mumps, rubella) 

Figure 37.3 

49

Mumps 

• caused by mumps virus 

• pleomorphic, enveloped 

virus 

• helical nucleocapsid 

• negative strand RNA 

Figure 37.4 

50

Rubella (German Measles) 

• caused by rubella virus 

• ssRNA virus 

• spread by respiratory droplets 

• congenital rubella syndrome 

• infection of pregnant women in 

first trimester 

• fetal death, premature delivery, 

and/or congenital defects 

• live attenuated vaccine: 

MMR- measles, mumps, rubella 

51

Human immunodeficiency virus (HIV) 

• 1983, HIV was correlated with 

AIDS (acquired immunodeficiency 

syndrome) 

• A retrovirus (an RNA virus) 

believed to have evolved in Africa 

from a monkey virus 

• 2006 CDC estimation: 

• ~ 1 million HIV infections in USA 

• Converging HIV and MDR-TB (multidrug 

resistance tuberculosis) Outbreaks 

Worsen

Figure 37.7 

HIV

Transmission 

• Acquired and passed from person to person 

• when infected blood, semen or vaginal secretions 

come in contact with uninfected person’s broken skin 

or mucous membranes 

• Groups most at risk in descending order 

• homosexuals 

• intravenous drug users 

• heterosexuals with drug users and prostitutes 

• children of infected mothers and breast-fed infants 

• transfusion patients and transplant recipients

HIV pathogenesis 

• Once inside host, HIV 

gp120 envelope protein 

binds to host CD4+ 

glycoprotein plasma 

membrane receptor on 

CD4 + cells 

Figure 37.8

Acquired Immune Deficiency 

Syndrome (AIDS) 

• caused by human immunodeficiency virus (HIV) 

• occurs world wide, causing the great pandemic of the 

second half of the twentieth century 

• retrovirus 

• theories on origin of disease 

• HIV-1 evolved from chimp virus SIVcpz 

• use of human blood products in chimps infected animals with 

HIV-1 precursor that evolved into SIVcpz

Course of Disease 

• some patients rapidly develop clinical 

AIDS; die within 2-3 years 

• some patients remain relatively healthy for 

at least 10 years post infection 

• in majority of patients HIV infection 

progresses to AIDS in 8-10 years

CDC classification for HIV-related stages 

• AIDS- fourth and last stage 

• immune system no longer able to defend 

against virus 

• definition of AIDS 

• all HIV-infected individuals who has fewer 

than 200 CD4 + T cells/microliter of blood or a 

CD4 + cell percentage of lymphocytes of less 

than 14

AIDS-related cancers 

• Kaposi’s sarcoma 

• caused by human herpesvirus 8 

• carcinoma of mouth and rectum 

• B-cell lymphomas

AIDS-related central nervous system disease 

• headaches, fever, subtle cognitive changes, 

abnormal reflexes, and ataxia 

• dementia and severe sensory and motor 

changes observed in advanced cases 

• autoimmune neuropathies, cerebrovascular 

disease, and brain tumors are common

61 

Viral Hepatitis 

• hepatitis 

• inflammation of liver 

• caused by different viruses 

• Epstein-Barr virus (EBV) 

• cytomegalovirus (CMV) 

• cause mild, self-resolving disease 

• no permanent hepatic damage 

• signs and symptoms include 

fatigue, nausea, and malaise 

• hepatotropic viruses (HAV, HBV, HCV, 

HDV, HEV, HGV, and ?)

Hepatotropic viruses 

Table 37.4

Acute viral Gastroenteritis 

• Food-borne and 

waterborne diseases 

• Inflammation of 

stomach or intestines 

• important disease of 

infants and children, 

leading cause of 

childhood death in 

developing countries 

• probably spread by 

fecal-oral route 

Figure 37.21 Rotavirus

Enterovirus 71 (1998~ ) 

• An RNA virus 

• Typical cold symptoms 

• mild enteric disease 

• hand, foot, and mouth disease 

• CNS (central nervous syndrome) diseases

Zoonotic (Animal-Borne) Diseases 

• human viral infections in animal reservoirs 

before transmission to and between humans 

• many are on Select Agents list as potential 

bioweapons 

• Ebola and Marburg viruses 

• hantaviruses 

• Lassa fever virus 

• Nipah virus 

bio-safety P4 level

Filoviridae- Marburg and Ebola virus 

• Ebola hemorrhagic fever 

• A severe and often fatal 

disease in human or 

nonhuman primates 

• 1 st recognition- 1976 

• 4 subtypes: 

• Humans- Ebola-Zaire, Ebola- 

Sudan, and Ebola-Ivory Coast 

• Nonhuman Primates- Ebola- 

Reston 

An RNA virus 

-1967, Marburg 

-1976, Ebola/Zaire 

66

Hantavirus Pulmonary Syndrome 

• An outbreak occurred in 

May 1993 in the Four 

Corners (New Mexico, Arizona, 

Colorado, and Utah) 

• The deer mouse- the 

principal carrier (climate 

changes) 

• Navajo Indian 

• No person to person spread 

• cause hemorrhagic fever 

67

Smallpox (Variola) 

• smallpox virus 

• A re-emerging disease: 

“Biological weapon” 

• transmitted by aerosol 

or contact 

• humans are only 

reservoir 

• 30% fatality 

68

Chapter 18

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?