Introduction to Viruses That Infect Humans:

. The DNA Viruses

 Viruses in Human Infections and Diseases

• DNA or RNA molecules are surrounded by

capsid; obligate parasites that enter a cell,
instruct its genetic and molecular
machinery to produce and release new
viruses.
• All DNA viruses are double-stranded except
for parvoviruses, which have ssDNA.
• All RNA viruses are single-stranded except
for dsRNA reoviruses.

2
 Medical Considerations in Viral Diseases
• Viruses are limited to a particular host or cell type.
• Most DNA viruses are budded off the nucleus.
• Most RNA viruses multiply in and are released from the
cytoplasm.
• Viral infections range from asymptomatic to mild to life-
threatening.
• Many viruses are strictly human in origin, others are
zoonoses transmitted by vectors.

3
• Course of viral disease: invasion at portal of entry
and primary infection; some viruses replicate locally,
others enter the circulation and infect other tissues
• Common manifestations: rashes, fever, muscle
aches, respiratory involvement, swollen lymph
nodes
• Body defenses: combined action of interferon,
antibodies and cytotoxic T cells; frequently results in
lifelong immunity

4
• Many viral infections have rapid course; lytic cycle
• Some viruses establish long-term persistent
infections that last many years or a lifetime.
• 2 types of persistent infections:
– chronic infections – virus is detectable in tissue
samples, multiplying at a slow rate; symptoms mild or
absent
– latent infections – after a lytic cycle, virus enters a
dormant phase; generally not detectable, no
symptoms; can reactivate and result in recurrent
infections

5
• Some persistent viruses are oncogenic.
• Several viruses can cross the placenta
causing developmental disturbances and
permanent defects – teratogenic.
• Diagnosis of viral diseases – symptoms,
isolation in cell or animal culture,
serological tests for antibodies; some tests
for antigens

6
 Survey of DNA Viruses
• Animal viruses are categorized according to
nucleic acid, capsid, and presence or
absence of envelope.
• 7 DNA families, 15 RNA families
• DNA viruses causing human disease:
– enveloped DNA viruses
– nonenveloped DNA viruses
– nonenveloped ssDNA viruses

7
Insert Table 24.1
DNA viruses

8
Enveloped DNA Viruses

9
Poxviruses: Classification and Structure
• Produce eruptive skin pustules called pocks or pox,
that leave scars
• Largest and most complex animal viruses
• Have the largest genome of all viruses
• dsDNA
• Multiply in cytoplasm in factory areas
– variola – cause of smallpox
– vaccinia – closely related virus used in vaccines
– monkeypox
– cowpox

10
Insert figure 24.1
poxviruses

11
 Smallpox
• First disease to be eliminated by vaccination
• Exposure through inhalation or skin contact
• Infection associated with fever, malaise,
prostration, and a rash
– variola major – highly virulent, caused toxemia, shock,
and intravascular coagulation
– variola minor –less virulent
• Routine vaccination ended in U.S. in 1972.
• Vaccine reintroduced in 2002 for military and
medical personnel

12
 Other Poxviruses
• Many mammalian groups host some poxvirus –
cowpox, rabbitpox, mousepox, elephantpox.
• Humans are susceptible to monkeypox and
cowpox.
• Monkeypox in humans – skin pocks, fever, swollen
lymph nodes
• Cowpox in humans – rare, usually confined to
hands; other cutaneous sites can be involved

13
 The Herpesviruses: Common, Persistent
Human Viruses
• All members show latency and cause recurrent
infection; viral DNA forms episome.
• Clinical complications of latency and recurrent
infections become more severe with advancing age,
cancer chemotherapy, or other conditions that
compromise the immune defenses.
• Common and serious opportunists among AIDS
patients
• Large enveloped icosahedral dsDNA
• Replicates within nucleus

14
Insert figure 24.5
herpesvirus

15
 Herpesviruses
• Large family; 8 infect humans
HSV-1 – herpes simplex 1
HSV-2 - herpes simplex 2
VZV – varicella zoster virus
CMV - cytomegalovirus
EBV – Epstein-Barr virus
HHV-6 – herpevirus 6 - roseola
HHV-7 - herpevirus 7
HHV-8 - herpevirus 8

16
 Herpes Simplex Viruses
• Humans susceptible to 2 varieties
• HSV-1- usually lesions on the oropharynx,
cold sores, fever blisters
– occurs in early childhood
• HSV-2 - lesions on the genitalia, possibly
oral
– occurs in ages 14-29
– can be spread without visible lesions

17
Insert Table 24.2
Herpes 1 and 2 comparison

18
 Epidemiology
• Transmission by direct exposure to secretions
containing the virus; active lesions most significant
source; genital herpes can be transmitted in the
absence of lesions
• HSV multiplies in sensory neurons, moves to ganglia
– HSV-1 enters 5th cranial nerve
– HSV-2 enters lumbosacral spinal nerve trunk ganglia
• Recurrent infection is triggered by various stimuli –
fever, UV radiation, stress, mechanical injury.
• Newly formed viruses migrate to body surface,
producing a local skin or membrane lesion.
19
 Insert figure 24.6
Latency and routes of recurrence

20
 Herpes of the Newborn
• HSV-1 and HSV-2
• Potentially fatal in the neonate and fetus
• Infant contaminated by mother before or
during birth; hand transmission by mother
to infant
• Infection of mouth, skin, eyes, CNS
• Preventative screening of pregnant women;
delivery by C-section if outbreak at the time
of birth

21
 Diagnosis, Treatment, and Control of
Herpes Simplex
• Vesicles and exudate are typical diagnostic
symptoms, scrapings from base of lesions
showing giant cells, culture and specific tests
for diagnosing severe or disseminated HSV;
direct fluorescent antibody tests
• Treatment: acyclovir, famciclovir, valacyclovir;
topical medications

22
 Varicella-Zoster Virus (VZV)
• Causes chickenpox and shingles
• Humans only natural host
• Transmitted by respiratory droplets and contact
• Primary infection – chickenpox – characteristic vesicles
• Virus enters neurons and remains latent
• Later, reactivation of the virus results in shingles with
vesicles localized to distinctive areas, dermatomes.
• More common in older patients
• Treatment: treat symptoms in uncomplicated
infections; acyclovir, famciclovir, interferon for
systemic disease
• Live attenuated vaccine for chickenpox and shingles

23
Insert figure 24.12
VZV relationship

24
 The Cytomegalovirus Group
• Cytomegaloviruses – CMV
• Produce giant cells with nuclear and cytoplasmic
inclusions
• Transmitted in saliva, respiratory mucus, breastmilk,
urine, semen, cervical secretions
• Commonly latent in various tissues
• Most infections are asymptomatic.
• 3 groups develop a more virulent form of disease:
fetuses, newborns, immunodeficient adults.

25
 Cytomegalovirus
• Newborns may exhibit enlarged liver and spleen, jaundice,
capillary bleeding microcephaly, and ocular inflammation; may be
fatal.
– Babies who survive develop neurological sequelae, hearing, visual
disturbances and mental retardation.
• Perinatal CMV infection – mostly asymptomatic, or pneumonitis,
and a mononucleosis-like syndrome
• AIDS patients – CMV mononucleosis, disseminated CMV, retinitis,
• Transplant patients - pneumonitis, hepatitis, myocarditis,
meningoencephalitis
• Treatment reserved for immunocompromised - ganciclovir,
foscarnet

26
 Epstein-Barr Virus (EBV)
• Ubiquitous virus; infects lymphoid tissue and salivary
glands
• Transmission – direct, oral contact and contamination
with saliva
• In industrialized countries, college-age population is
vulnerable to infectious mononucleosis (mono or
kissing disease).
• By mid-life, 90-95% of all people are infected.
• Infectious mononucleosis – sore throat, high fever,
cervical lymphadenopathy; develop after 30-50 day
incubation
• Dormancy in B cells; reactivated; may be
asymptomatic
27
 Tumors and Other Complications
Associated with EBV
• Burkitt lymphoma – B cell malignancy; usually
develops in jaw and grossly swells the cheek; central
African children 4-8 years old; may be associated with
chronic coinfections with malaria, etc.
• Nasopharyngeal carcinoma – malignancy of epithelial
cells; occurs in older Chinese and African men
• Anyone with an immune deficiency is highly
susceptible to EBV.

28
 Diagnosis, Treatment and Prevention
• Differential blood count shows lymphocytosis,
neutropenia, and large atypical lymphocytes;
serological assays to detect antibodies and antigen.
• Treatment directed at relief of symptoms of fever and
sore throat
• Disseminated disease may be treated with IV gamma
globulin, interferon, acyclovir, and monoclonal
antibodies.

29
Other Herpesviruses and the Cancer Connection
• Human herpes virus 6 (HHV-6)-human T-lymphotropic
virus
• Transmitted by close contact with saliva and other
secretions; very common
• Causes roseola, an acute febrile disease in babies 2-12
months; begins with fever, followed by a faint
maculopapular rash; usually self-limited
• Adults may get mono-like symptoms,
lymphadenopathy and hepatitis
• Can cause encephalitis, cancer–Hodgkin lymphoma,
oral carcinoma, certain T-cell leukemias

30
• HHV-7 is closely related to HHV-6 and
causes similar diseases.
• Kaposi’s sarcoma-associated virus or HHV-8
is linked with common tumor of AIDS
patients; also may be involved in multiple
myeloma.

31
 The Viral Agents of Hepatitis
• Hepatitis – an inflammatory disease of liver
cells that may result from several viruses
• Interferes with liver’s excretion of bile
pigments, bilirubin accumulates in blood and
tissues causing jaundice, a yellow tinge in skin
and eyes
• 3 principal viruses involved in hepatitis:
– hepatitis B, hepatitis A (RNA virus), hepatitis C
(RNA virus)

32
Insert Table 24.3
Major hepatitis viruses

33
 Hepadnaviruses
• Enveloped DNA viruses
• Never been grown in tissue culture
• Unusual genome containing both double and single
stranded DNA
• Tropism for liver
• Hepatitis B virus causes hepatitis and can be a factor
in liver cancer.
• Other members cause hepatitis in woodchucks,
ground squirrels, and Peking ducks.

34
 Hepatitis B Virus and Disease
• Multiplies exclusively in the liver, which continuously
seeds blood with viruses - chronic
• 107 virions/mL blood
• Minute amounts of blood, blood products can transmit
infection; sexually transmitted
• High incidence among homosexuals and drug addicts
• Can become a chronic infection
• Increases risk of liver cancer – hepatocellular carcinoma

35
Insert figure 24.21
Clinical features of hepatitis B

36
 Pathogenesis of Hepatitis B Virus
• Virus enters through break in skin or mucous
membrane or by injection into bloodstream.
• Reaches liver cells, multiplies and releases viruses into
blood; average 7 week incubation
• Most exhibit few overt symptoms and eventually
develop HBV immunity.
• Some experience malaise, fever, chills, anorexia,
abdominal discomfort and diarrhea.
• Fever, jaundice, rash, and arthritis are common.
• Small number of patients develop chronic liver disease
– necrosis and cirrhosis.
37
 Diagnosis and Management of Hepatitis B

• Diagnosis based on examination of risk factors,

serological tests to detect viral antibodies or
antigen; radioimmunoassay and ELISA tests for
surface antigens
• Screening of blood for transfusion, semen for
sperm banks, organs for transplant, and routine
prenatal testing of all pregnant women
• Mild cases managed by treatment of symptoms
and supportive care; chronic infections treated
with interferon
38
• Passive immunization with HBIG for persons
exposed, or possibly exposed, including
neonates born to infected mothers
• Primary prevention is vaccination for high
risk individuals and encouraged for all
newborns and infants.
– vaccines derived from surface antigen from
cloned yeast – 3 doses with boosters
– vaccine derived from purified sterile antigen
extracted from carrier blood; mainly for people
who have yeast allergies

39
Nonenveloped DNA Viruses

40
 The Adenoviruses
• Nonenveloped, ds DNA
• 30 types associated with human disease
• Infect lymphoid tissue, respiratory and intestinal
epithelia and conjunctiva
• Oncogenic in animals, not in humans
• Spread by respiratory and ocular secretions
• Causes colds, pharyngitis, conjunctivitis,
keratoconjunctivitis, acute hemorrhagic cystitis
• Severe cases treated with interferon
• Inactivated polyvalent vaccine
41
 Papilloma and Polyoma Viruses
• Small, nonenveloped dsDNA
• Circular DNA
• Cause persistent infections and tumors

42
 Human Papillomavirus
• Papilloma – benign, squamous epithelial growth,
wart or verruca
• Caused by 100 different strains of HPV
• Common seed warts – painless, elevated, rough
growth; on fingers, etc.
• Plantar warts – deep, painful; on soles of feet
• Genital warts – most common STD in U.S.;
morphology ranges from tiny, flat, inconspicuous
bumps to extensive, branching, cauliflower-like
masses
• Transmissible through direct contact or
contaminated fomites; incubation – 2 weeks to more
than a year
43
• Nine HPV types increase risk for developing
reproductive cancer; 2 account for 70% of metastatic
tumors.
• Early detection through inspection of genitals,
women Pap smear to screen for abnormal cervical
cells
• Most common warts regress over time; they can be
removed by direct chemical application of
podophyllin and physical removal by cauterization,
freezing, or laser surgery.
• Warts can recur.
• Two vaccines scheduled to be released in 2007

44
 Polyomaviruses
• Induce tumors in experimental animals
• JC and BK viruses most important human polyomas
• Common throughout the world
• Majority of infections are asymptomatic or mild
• Not much is known.
• BK infection in renal transplants causes complications
in urinary function.
• Progressive multifocal leukoencephalopathy (PML) is
an uncommon fatal infection by JC.

45
 Parvoviruses
• Nonenveloped icosahedral, ssDNA
• Small diameter and genome size
• Causes distemper in cats, enteric disease in dogs, fatal
cardiac infection in puppies
• B19 cause of erythema infectiosum (fifth disease);
rash of childhood
– Children may have fever and rash on cheeks.
– Severe fatal anemia can result if pregnant woman transmits
virus to fetus.
• Adeno-associated virus (AAV) is a defective virus; it
cannot replicate in host cell without adenovirus.
46
The. RNA Viruses That Infect Humans
 RNA Viruses
Assigned to one of 12 families based on
envelope, capsid, and nature of RNA genome

48
Insert Table 25.1
RNA viruses

49
Enveloped Segmented Single-Stranded RNA
Viruses

50
 The Biology of Orthomyxoviruses:
Influenza
• ssRNA consists of 10 genes encoded on 8 separate
RNA segments.
• 3 distinct influenza virus types: A, B, C; Type A causes
most infections
• Virus attaches to, and multiplies in, the cells of the
respiratory tract; finished viruses are assembled and
budded off.

51
Insert figure 25.1
Influenza cycle

52
• Key to influenza are glycoprotein spikes –
– hemagglutinin (H) – 15 different subtypes; most important
virulence factor; binds to host cells
– neuraminidase (N) – 9 subtypes – hydrolyzes mucus and
assists viral budding and release
• Both glycoproteins frequently undergo genetic
changes decreasing the effectiveness of the host
immune response.
• Constant mutation is called, antigenic drift - gradually
change their amino acid composition
• Antigenic shift – one of the genes or RNA strands is
substituted with a gene or strand from another
influenza virus from a different animal host

53
Insert figure 25.3
Antigenic shift

54
Influenza B
• Not known to undergo antigenic shift

Influenza C
• Known to cause only minor respiratory
disease; probably not involved in epidemics

55
 Influenza A
• Acute, highly contagious respiratory illness
• Seasonal, pandemics; among top 10 causes of death
in U.S.- most commonly among elderly and small
children
• Respiratory transmission
• Binds to ciliated cells of respiratory mucosa
• Causes rapid shedding of cells, stripping the
respiratory epithelium; severe inflammation
• Fever, headache, myalgia, pharyngeal pain, shortness
of breath, coughing
• Weakened host defenses predispose patients to
secondary bacterial infections, especially pneumonia.
56
 Diagnosis, Treatment, Prevention
• Rapid immunofluorescence tests to detect
antigens in a pharyngeal specimen; serological
testing to screen for antibody titer
• Treatment: control symptoms; amantadine,
rimantadine, zanamivir (Relenza) and
oseltamivir (Tamiflu)
• Flu virus has developed high rate of resistance
to amantadine and rimantadine.
• Annual trivalent vaccine recommended

57
 Bunyaviruses and Arenaviruses
• Transmitted zoonotically; cause periodic epidemics;
extremely dangerous; biosafety level 4 viruses
Bunyaviruses – transmitted by insects and ticks
– California encephalitis, Rift Valley fever, Korean hemorrhagic
fever
– American bunyavirus is a hantavirus, Sin Nombre – emerging
disease; high fever, lung, edema, and pulmonary failure; 33%
mortality rate
• carried by deer and harvest mice; transmitted via airborne
dried animal waste
Arenaviruses
• Lassa fever, Argentine hemorrhagic fever, Bolivian hemorrhagic
fever, and Lymphocytic chroiomeningitis
• Closely associated with rodent host
• Transmission through aerosols and contact
58
Enveloped Nonsegmented ssRNA Viruses

59
 Paramyxoviruses
Paramyxoviruses (parainfluenza, mumps virus)
Morbillivirus (measles virus)
Pnuemonovirus (respiratory syncytia virus)
• Respiratory transmission
• Envelope has HN and specialized F spikes that
initiate cell-to-cell fusion.
• Fusion with neighboring cells – syncytium or
multinucleate giant cells form

60
Insert figure 25.5
Effects of paramyxoviruses

61
 Parainfluenza
• Widespread as influenza but more benign
• Respiratory transmission
• Seen mostly in children
• Minor cold, bronchitis, bronchopneumonia,
croup
• No specific treatment available; supportive
therapy

62
 Mumps
• Epidemic parotitis; self-limited, associated with
painful swelling of parotid salivary glands
• Humans are the only reservoir.
• 40% of infections are subclinical; long-term immunity.
• 300 cases in U.S./year
• Incubation 2-3 weeks fever, muscle pain and malaise,
classic swelling of one or both cheeks
• Usually uncomplicated invasion of other organs; in
20-30% of infected adult males, epididymis and testes
become infected; sterility is rare
• Symptomatic treatment
• Live attenuated vaccine MMR
63
 Measles
• Caused by Morbillivirus
• Also known as red measles and rubeola
• Different from German measles
• Very contagious; transmitted by respiratory aerosols
• Humans are the only reservoir.
• Less than 100 cases/yr in U.S.; frequent cause of
death worldwide
• Virus invades respiratory tract.
• Sore throat, dry cough, headache, conjunctivitis,
lymphadenitis, fever, Koplik spots – oral lesions
• Exanthem

64
 Measles
• Most serious complication is subacute sclerosing
panencephalitis (SSPE), a progressive neurological
degeneration of the cerebral cortex, white matter
and brain stem.
• 1 case in a million infections
• Involves a defective virus spreading through the
brain by cell fusion and destroys cells
• Leads to coma and death in months or years
• Attenuated viral vaccine MMR

65
 Respiratory Syncytial Virus (RSV)
• Also called Pneumovirus
• Infects upper respiratory tract and produces giant
multinucleate cells
• Most prevalent cause of respiratory infection in
children 6 months or younger; most susceptible to
serious disease
• Epithelia of nose and eye portal of entry; replicates in
nasopharynx
• Fever, rhinitis, wheezing, otitis, croup
• Treatment: synagis, a monoclonal antibody that blocks
attachment, ribavirin
66
 Rabies
• Rhabdovirus family; genus Lyssavirus
• Enveloped, bullet-shaped virions
• Slow, progressive zoonotic disease
• Primary reservoirs are wild mammals; it can be
spread by both wild and domestic mammals by bites,
scratches, and inhalation of droplets.

67
Insert figure 25.8
Structure of rabies virus

68
 Rabies
• Virus enters through bite, grows at trauma site for a
week and multiplies, then enters nerve endings and
advances toward the ganglia, spinal cord and brain.
• Infection cycle completed when virus replicates in the
salivary glands
Clinical phases of rabies:
• Prodromal phase – fever, nausea, vomiting, headache,
fatigue; some experience pain, burning, tingling
sensations at site of wound
• Furious phase – agitation, disorientation, seizures,
twitching, hydrophobia
• Dumb phase – paralyzed, disoriented, stuporous
• Progress to coma phase, resulting in death
69
70
• Often diagnosed at autopsy – intracellular inclusions
(Negri bodies) in nervous tissue
• Bite from wild or stray animals demands assessment
of the animal, meticulous wound care, and specific
treatment.
• Preventive therapy initiated if signs of rabies appear
• Treatment – passive and active postexposure
immunization
– infuse the wound with human rabies immune globulin
(HRIG) and globulin; vaccination with human diploid cell
vaccine (HDCV), an inactivated vaccine given in 6 doses
with 2 boosters
• Control - vaccination of domestic animals,
elimination of strays, and strict quarantine practices
– live oral vaccine incorporated into bait for wild animals

71
 Coronaviruses
• Relatively large RNA viruses with distinctively
spaced spikes on their envelopes
• Common in domesticated animals
• 3 types of human coronaviruses have been
characterized:
– HCV causes a cold
– an enteric virus
– Severe Acute Respiratory Syndrome (SARS)
• airborne transmission
• 10% of cases fatal

72
 Severe Acute Respiratory Syndrome-
Associated Coronavirus (SARS)
• Newly emerging disease – 2002
• Transmitted through droplet or direct contact
• Fever, body aches, and malaise
• May or may not experience respiratory symptoms
with breathing problems; severe cases can result in
respiratory distress and death
• Diagnosis relies on exclusion of other likely agents.
• Treatment is supportive.

73
 Rubella
• Caused by Rubivirus, a Togavirus
• ssRNA with a loose envelope
• German measles
• Endemic disease
• Most cases reported are adolescents and
young adults.
• Transmitted through contact with
respiratory secretions

74
 Rubella
Two clinical forms:
• Postnatal rubella – malaise, fever, sore throat,
lymphadenopathy, rash, generally mild, lasting
about 3 days
• Congenital rubella – infection during 1st trimester
most likely to induce miscarriage or multiple
defects such as cardiac abnormalities, ocular
lesions, deafness, mental and physical retardation
• Diagnosis based on serological testing
• No specific treatment available
• Attenuated viral vaccine MMR

75
 Hepatitis C Virus (HCV)
• Flavivirus; non-A non-B virus
• Acquired through blood contact – blood transfusions,
needle sharing by drug abusers
• Infections with varying characteristics -75-85% will
remain infected indefinitely; possible to have severe
symptoms without permanent liver damage; more
common to have chronic liver disease, without overt
symptoms
• Cancer may also result from chronic HCV infection.
• Treatment with interferon and ribavirin to lessen liver
damage; no cure
• No vaccine

76
 Arboviruses: Viruses Spread by
Arthropod Vectors

• Mosquitoes, ticks, flies, and gnats

• 400 viruses
• Togaviruses, flaviviruses, some bunyaviruses
and reoviruses
• Most illnesses caused by these viruses are mild
fevers; some may cause severe encephalitis,
and life-threatening hemorrhagic fever.

77
 The Influence of the Vector
• Vectors and viruses tend to be clustered in the
tropics and subtropics; many temperate zones
have periodic epidemics.
• Arbovirus life cycles are closely tied to the ecology
of the vectors.
• Infections show a peak incidence when the
arthropod is actively feeding and reproducing.
• Humans can serve as dead-end, accidental hosts
or they can be a maintenance reservoir.
• Controlling the vector controls the disease.
78
Insert figure 25.12
Worldwide distribution

79
 General Characteristics of Arbovirus
Infections
• Acute arbovirus infection may result in
undifferentiated mild fever with rash; no long-term
effects; prominent symptoms are fever, headache,
myalgia, joint stiffness, rash.
• Viral encephalitis – brain, meninges, and spinal cord
are involved; convulsions, tremor, paralysis, loss of
coordination, memory deficits, changes in speech and
personality, coma; survivors may experience
permanent brain damage
• Treatment is supportive.
• Vaccine for yellow fever, those traveling to tropics,
those in high risk occupations
80
• Colorado tick fever (CTF) – most common tick-borne
viral fever in U.S.; Rocky Mountain states
• Western equine encephalitis (WEE) – western U.S.
and Canada; extremely dangerous to infants and
small children
• Eastern equine encephalitis (EEE) – eastern U.S. and
Canada
• California encephalitis – 2 different strains:
– California strain – western states; little human impact
– LaCrosse strain – eastern U.S. and Canada; prevalent cause
of viral encephalitis
• St. Louis encephalitis (SLE) – most common of all in
America; epidemics in midwestern and southern
states; inapparent infections are very common
• West Nile encephalitis
81
 Hemorrhagic Fevers
Yellow fever – eliminated in U.S.
• Two patterns of transmission:
– urban cycle – humans and mosquitoes, Aedes aegypti
– sylvan cycle - forest monkeys and mosquitoes; South
America
• Acute fever, headache, muscle pain; may progress to
oral hemorrhage, nosebleed, vomiting, jaundice, and
liver and kidney damage; significant mortality rate
Dengue fever - flavivirus carried by Aedes mosquito; not
in U.S.; usually mild infection
– dengue hemorrhagic shock syndrome, breakbone fever -
extreme muscle and joint pain; can be fatal

82
 HIV Infections and AIDS
• Human immunodeficiency virus
• Acquired immunodeficiency syndrome
• First emerged in early 1980s
• HIV-1 may have originated from a chimpanzee
virus.
• 1959 first documented case of AIDS

83
 Causative Agent
• Retrovirus, genus Lentivirus
• Encode reverse transcriptase enzyme which
makes a double stranded DNA from the single-
stranded RNA genome
• Viral genes permanently integrated into host DNA
• Human Immunodeficiency Virus (HIV) the cause
of Acquired Immunodeficiency Syndrome (AIDS)
• HIV-1 and HIV-2
• T-cell lymphotropic viruses I and II – leukemia and
lymphoma
• HIV can only infect host cells that have the
required CD4 marker plus a coreceptor.

84
Insert figure 25.13
HIV general structure

85
 Epidemiology of HIV Infections
• Transmission occurs by direct and specific
routes: mainly through sexual intercourse
and transfer of blood or blood products;
babies can be infected before or during birth,
and from breast feeding.
• HIV does not survive long outside of the
body.

86
Insert figure 25.14
HIV routes of infection

87
• First nationally notifiable in 1984
• 6th most common cause of death among people
aged 25-44 years in the U.S.
• Men account for 70% of new infections.
• Anal sex provides an entrance for the virus.
• IV drug abusers can be HIV carriers; significant factor
in spread to heterosexual population
• In 2006, the number of infected individuals
worldwide is estimated to be 45 million with ~1
million in the U.S.

88
Insert figure 25.15
Patterns of HIV infections

89
 Pathogenesis and Virulence Factors of
HIV
• HIV enters through mucous membrane or skin and
travels to dendritic phagocytes beneath the
epithelium, multiplies and is shed.
• Virus is taken up and amplified by macrophages in
the skin, lymph organs, bone marrow, and blood.
• HIV attaches to CD4 and coreceptor; HIV fuses
with cell membrane.
• Reverse transcriptase makes a DNA copy of RNA.
• Viral DNA is integrated into host chromosome
(provirus).
• Can produce a lytic infection or remain latent

90
Insert figure 25.16
Multiplication of HIV

91
Primary effects of HIV infection:
– extreme leukopenia – lymphocytes in particular
– formation of giant T cells and other syncytia
allowing the virus to spread directly from cell to
cell
– Infected macrophages release the virus in central
nervous system, with toxic effect, inflammation.
Secondary effects of HIV:
– Destruction on CD4 lymphocytes allows for
opportunistic infections and malignancies.

92
Signs and Symptoms of HIV Infections and
AIDS
• Symptoms of HIV are directly related to viral blood
level and level of T cells.
• Initial infection – mononucleosis-like symptoms that
soon disappear
• Asymptomatic phase 2-15 years (avg. 10)
• Antibodies are detectable 8-16 weeks after infection.
• HIV destroys the immune system.
• When T4 cell levels fall below 200/mL AIDS symptoms
appear including fever, swollen lymph nodes,
diarrhea, weight loss, neurological symptoms,
opportunistic infections and cancers.

93
Insert figure 25.17
HIV timeline

94
Insert figure 25.18
Antigen/antibody changes

95
 Diagnosis of HIV Infection
• Testing based on detection of antibodies specific to
the virus in serum or other fluids; done at 2 levels
• Initial screening
– ELISA, latex agglutination and rapid antibody tests
– rapid results but may result in false positives
• Follow up with Western blot analysis to rule out false
positives
• False negatives can also occur; persons who may have
been exposed should be tested a second time 3-6
months later.
96
Diagnosis of AIDS is made when a person meets the
criteria:
1. Positive for the virus, and
2. They fulfill one of the additional criteria:
• They have a CD4 count of fewer than 200 cells/ml of
blood.
• Their CD4 cells account for fewer than14% of all
lymphocytes.
• They experience one or more of a CDC-provided list
of AIDS-defining illnesses.

97
Insert Table 25.A page 776
AIDS-defining illnesses

98
 Preventing and Treating HIV
• No vaccine available
– monogamous sexual relationships
– condoms
– universal precautions
• No cure; therapies slow down the progress of the
disease or diminish the symptoms
– inhibit viral enzymes: reverse transcriptase, protease,
integrase
– inhibit fusion
– inhibit viral translation
– highly active anti-retroviral therapy

99
100
 Adult T-Cell Leukemia and Hairy-Cell
Leukemia
Leukemia is a malignant disease of the white blood cell
forming elements in bone marrow; bruising or
bleeding, paleness, fatigue and recurring minor
infections occur.
• 2 leukemias are thought to be viral:
– Adult T-Cell leukemia - HTLV-I; signs also include
cutaneous T-cell lymphoma with lymphadenopathy and
dissemination of the tumors to other organs
– Hairy-cell leukemia – HTLV II; rare form of cancer; fine
cytoplasmic projections that resemble hairs
101
Nonenveloped Nonsegmented ssRNA Viruses:
Picornaviruses and Caliciviruses
• Picornaviruses
– Enterovirus – poliovirus

102
 Poliovirus and Poliomyelitis
Poliomyelitis (polio) – acute enteroviral infection of the
spinal cord that can cause neuromuscular paralysis
• Poliovirus – naked capsid; resistant to acid, bile, and
detergents; can survive stomach acids when ingested
• Worldwide vaccination programs have reduced the
number of cases; eradication is expected.

103
Insert figure 25.22
Picornavirus structure

104
• Transmitted by fecal-oral route
• Polioviruses adhere to receptors of mucosal
cells in oropharynx and intestine, multiply in
number and shed in throat and feces, some
leak into blood.
• Most infections are short-term, mild viremia.
• Some develop mild nonspecific symptoms of
fever, headache, nausea, sore throat, and
myalgia.
• If viremia persists, virus spreads to spinal cord
and brain.

105
• If nervous tissue is infected but not
destroyed – muscle pain and spasm,
meningeal inflammation, and vague
hypersensitivity
• Invasion of motor neurons causes flaccid
paralysis.
• Decades later post-polio syndrome (PPS) –
progressive muscle deterioration; occurs in
25-50% of patients infected with polioviruses
in childhood

106
107
 Treatment and Prevention
• Treatment is largely supportive for pain and
suffering; respiratory failure may require
artificial ventilation; physical therapy may be
needed.
• Prevention is vaccination.
• Inactivated polio vaccine (IPV) Salk vaccine
• Oral polio vaccine (OPV) Sabin vaccine,
attenuated virus – no longer recommended in
the U.S.
• Worldwide eradication anticipated by 2008
108
Hepatitis A Virus and Infectious Hepatitis
• Cubical picornavirus relatively resistant to heat
and acid
• Not carried chronically, principal reservoirs are
asymptomatic, short-term carriers or people
with clinical disease
• Fecal-oral transmission; multiplies in small
intestine and enters the blood and is carried to
the liver
• Most infections subclinical or vague, flu-like
symptoms occur; jaundice is seldom present
109
• No specific treatment once the symptoms
begin
• Inactivated viral vaccine
• Attenuated viral vaccine
• Pooled immune serum globulin for those
entering into endemic areas

110
 Human Rhinovirus (HRV)
• More than 110 serotypes associated with the
common cold
• Sensitive to acidic environments; optimum
temperature is 33oC
• Unique molecular surface makes development
of a vaccine unlikely.
• Endemic with many strains circulating in the
population at one time; acquired from
contaminated hands and fomites
111
• Headache, chills, fatigue, sore throat,
cough, nasal drainage
• Treat the symptoms
• Handwashing and care in handling nasal
secretions

112
 Caliciviruses
• Norwalk agent best known; believed to cause
1/3rd of all viral gastroenteritis cases
• Transmitted by fecal-oral route
• Infection in all ages at any time of year
• Acute onset, nausea, vomiting, cramps,
diarrhea, chills
• Rapid and complete recovery

113
 Nonenveloped Segmented dsRNA
Viruses: Reoviruses
Unusual double-stranded RNA genome
Two best known:
• Rotavirus – oral-fecal transmission; primary viral
cause of mortality and morbidity resulting from
diarrhea in infants and children
– treatment with rehydration and electrolyte
replacement
• Reovirus – cold-like upper respiratory infection,
enteritis

114
Prions and Spongiform Encephalopathies
Prions – proteinaceous infectious particles; highly
resistant to chemicals, radiation, and heat
• Cause transmissible spongiform
encephalopathies (TSEs) in humans and
animals
• Neurodegenerative diseases with long
incubation periods

115
End