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Virology

General Characteristics
 Smallest infectious agents (20-300 nm)
 Contains only one kind of nucleic acid (RNA or DNA) as their genome
 Most can only be seen with the use of Electron Microscope
 Obligate intracellular parasites. They lack the chemical machinery for generating and synthesizing large
molecules. Viruses therefore, must find an appropriate host cell in which they can replicate

Viral Structure
1.) Nucleic Acid Genome
 Either DNA or RNA  double stranded or single stranded
 RNA: positive sense (+) or negative sense (-)
Viruses with ssRNA are divided into two groups:
Positive sense – if the RNA of the genome has the same polarity as the viral mRNA and can
thus function directly as messenger RNA.
Negative sense – if the genome RNA has the polarity opposite to that of mRNA, and therefore
cannot be translated into proteins until it has first been transcribed into a complementary strand.

2.) Capsid
 Virus coded proteins that encloses the nucleic acid of the virus and determines its antigenicity. It
can resist temperature, pH and other environmental fluctuations.
Capsomeres – protein subunits that makes up a capsid.
Nucleocapsid – the capsid with its enclosed genome
Spikes – special capsid proteins present in some viruses that helps attach the virus to the host
cell and facilitate penetration of the cell
Capsid symmetry:
Icosahedral – cubic symmetry, has 20 triangular faces and 12 corners
Helical – it is a tightly wound coil resembling a corkscrew or spring
Complex – viruses which have a combination of icosahedral and helical

3.) Envelope
 A lipid-containing membrane that surrounds some virus particles
 It is acquired during viral maturation by a budding process through a cellular membrane.
 May or may NOT be present in a virus (“naked viruses”)

Host Range and Tissue specificity


Host range – refers to what organisms (hosts) the virus can infect and it is based on a virus’
capsid structure.
Examples:
A bacteriophage only infects bacterial species
Smallpox viruses only infects humans

Tissue specificity – tissue tropism, the limitation of many viruses in which they can only infect
certain cell types or tissues within a multicellular plant or animal.
Examples:
HIV primarily infects a specific group of white blood cells called T helper cells
Rabies virus is best at infecting cells of the nervous system and brain

 If a potential host cell lacks the appropriate receptor or the virus lacks the complementary protein, the
virus usually cannot bind to or infect that cell.

Replication Cycle
1.) Attachment – interaction of the virus with a specific receptor site on the surface of host cell.
2.) Penetration and uncoating
 Viruses adsorbed to the cell surface receptors then penetrate into the cell by the following
mechanisms:
Endocytosis – Naked viruses
Fusion with the cell membrane – Enveloped viruses
 Uncoating involves the release of nucleic acid from the capsid
3.) Biosynthesis

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 Proliferation of the viral components: virus-coded synthesis of capsid and noncapsid proteins,
replication of nucleic acid by viral and cellular enzymes
4.) Assembly – in this step, the viral capsid proteins and genomes (present in multiple copies after
replication) are assembled into new, infectious virus particles (virion). In some viral species these
particles are covered by an envelope.
Virion – A mature viral particle, composed of nucleic acid core, capsid and in some envelope ready for
release from the cell.
5.) Release – final stage
Naked viruses leave the cell when the cell membrane ruptures (lysis)
Enveloped viruses fuses with the plasma membrane, releasing the virion (budding)

Method of Cultivation
 Chick Embryo
– Introduced by Alice M. Woodruff and Ernest W. Goodpasture in 1931
– The shell of the egg was a natural culture dish containing nutrient medium, and viruses multiplied
within the chick embryo tissues.
 Cell culture

Classification of Viruses

DNA Viruses

Enveloped Naked
Herpesviridae Adenoviridae
HepaDNAviridae Papoviridae
Poxviridae Parvoviridae

Mnemonics: HeHePox Mnemonics: APaPar

General Characteristics of DNA Viruses


 Double stranded except Parvoviruses
 Icosahedral except Poxvirus
 Replicates in nucleus except Poxvirus

1.) Herpesviridae

Properties:
 Large viruses with an icosahedral symmetry and a double-stranded DNA genome
 Members vary widely in biologic properties
 Establish lifelong latent infections
– Possess a latent stage of the infection where they are found in neurons especially in the ganglia
– Affecting immunocompromised hosts producing severe diseases
 Diseases associated with primary infection and reactivated infection may vary markedly
 Cytopathic effects
 Controlled by T-cells
Classes:
 α herpes – HSV-1, HSV-2, VZV
 Β herpes – CMV
 δ herpes – EBV, HHV-6, HHV-7, HHV-8, BV

Agents:

1.1 Herpes Simplex Virus


 Grow rapidly and highly cytolytic (necrosis of infected cells with inflammatory response)
 Establish latent infections in nerve cells; recurrences are common
 Modes of transmission:
– Contact thru mucosal surface or broken skin
– Respiratory droplets
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– Direct contact with infected saliva
– Genital routes: sexual transmission and normal delivery
 Treatment
– Acyclovir, Valacyclovir, Vidarabine

 Herpes Simplex Virus type 1 (HSV1)

Disease Characteristic/s Signs and Symptoms


Gingivostomatis Occurs primarily in children Swollen, tender gums with
involving buccal and gingival vesicular lesions in the mouth
mucosa of the mouth

Herpes simplex labialis “Fever blisters” or “Cold sores”


Milder, recurrent form
characterized by crops of vesicles
usually at the mucocutaneous
border of the lips

Keratoconjunctivitis Also known as “herpitic keratitis”


Recurrent form appears as
dendritic keratitis or corneal
ulcers or vesicles on the eyelids

Encephalitis Sporadic fatal form of fever, HA, vomiting, seizures and


encephalitis in US altered mental status
Necrotic lesions in one temporal
lobe of the brain

Traumatic Herpes (skin Herpetic whitlow - pustular


infections) lesion of the skin of the finger or
hand resulting from contact with
patient’s lesions
Herpes gladiatorum or Mat
herpes - bodies of wrestlers
Eczema herpeticum - HSV-1
infection in persons with chronic
eczema, can be fatal

 Herpes Simplex Virus type 2 (HSV2)

Usually associated with the STD form of Herpes

Genital herpes

- Painful vesicular lesions of the male (penis) and female genitals (cervix, vulva, vagina
and perineum) and anal area

Neonatal herpes

- Originates chiefly from contact with vesicular lesions within the birth canal

1.2 Varicella Zoster Virus (VZV)


 “Chicken pox”
 Mild in children and severe in adults
 Characterized by a generalized vesicular eruption of skin and mucous membranes (water-filled
vesicles) and fever
 Usually contagious during recovery period through the mucosa of the respiratory tract or conjunctiva

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Zoster Virus
 “Shingles”
 A reinfection characterized by localized painful skin lesions which manifest over a skin area
innervated by a single sensory neuron

Treatment and Prevention:


– Antiviral drugs like acyclovir, valacyclovir, famciclovir amd foscarnet
– Live attenuated VZV vaccine given in two shots during infancy

1.3 Cytomegalovirus
 Ubiquitous herpes viruses causing most congenital infections
 Produces giant multinucleated cells
 Transmission requires close person-to-person contact and by blood transfusion
 Virus is shed in urine, saliva, semen, breast milk, cervical secretions and in circulating WBCs
 Diseases:
- CMV mononucleosis (older children and adults)
- CMV infections that leads to pneumonia (immunocompromised hosts)
- Congenital and perinatal infections like
- Cytomegalic inclusion disease of newborns affecting CNS and reticuloendothelial
system
- Develops into CNS defects like severe hearing loss (deafness), ocular (CMV retinitis)
abnormalities and mental retardation
Treatment:
Ganciclovir for life-threatening CMV infections in immunocompromised hosts; CMV retinitis, esophagitis
and colitis; controls progressive hearing loss in neonates
Foscarnet the recommended treatment for CMV retinitis
Acyclovir and Valacyclovir in bone marrow and transplants patients

1.4 Ebstein Barr Virus (EBV)


 Causes “infectious mononucleosis”
– Also known as “kissing disease”
 Associated with cancer
– “Burkitt’s lymphoma” seen in African children (tumor of the jaw)
– Nasopharyngeal carcinoma, a cancer of epithelial cells and common in male Chinese people
– Oral hairy leukoplasia, a wart-like growth in tongue among AIDS patients

1.5 Human Herpes Virus 6 (HHV6)


 1st recognized in 1986 from peripheral blood mononuclear cells from patients with lymphoproliferative
disorders
 Interacts with with human CD46 T-cells
 Transmitted via oral secretions
 Affects early infancy causing the 6th disease or “roseola infantum” or “exanthem subitum”
 S/Sx are fever and skin rash

1.6 Human Herpes Virus 7 (HHV7)


 Isolated in 1990 from activated T-cells recovered from peripheral blood lymphocytes of healthy individuals
 Persistent infections are established in the salivary glands
 Transmitted via oral secretions
 Affects infants and children causing roseola infantum

1.7 Human Herpes Virus 8 (HHV8)


 A new herpesvirus detected in 1994
 Also known as “KSHV” (kaposi sarcoma-associated herpesvirus)
 Transmitted by contact with oral secretions, sexual contact, blood tranfusion, organ transplants and
through breast milk
 Treatment includes foscarnet, famciclovir, ganciclovir, cidofovir
1.8 B Virus
 Herpes B virus of Old World monkeys which is highly pathogenic for humans
 Usually results from monkey bite, also by respiratory route or ocular splash exposure
 Causes an acute ascending myelitis and encephalomyelitis
 Acyclovir is recommended immediately after exposure
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2. HepaDNAviridae (Hepa DNA virus)

Diseases:

2.1 Hepatitis B
 Serum Hepatitis
 Only Hepatitis virus with DNA Genome
 Normal virions consist of a nucleocapsid surrounded by a hepatitis B core antigen (HBcAg) and
envelope containing hepatitis B surface antigen (HBsAg).
 Transmission of hepatitis B usually involves direct or indirect contact with an infected body fluid such as
blood or semen.
 The final stages can be liver cirrhosis or hepatocellular carcinoma.

Serologic Exams for HBV


Dane Particles Mature Hepa B Virus
HBsAg (Hepa B Surface Antigen) Indicates infection
Anti-HBsAg (Antibody for Surface Antigen) Implies a certain state of immunity
HBcAg (Hepa B Core Antigen) Indicates an exposure to Hepa B
IgM Anti-HBcAg Immunoglobulin produced in response to acute
infection
IgG Anti HbcAg Immunoglobulin produced in response to chronic
infection
HbeAg (Envelope antigen) Indicates a highly infectious state

Anti-HBeAg (Antibody for HbeAg) Indicates a low infectious state

Hepatitis D
 Caused by two viruses: HBV and the hepatitis D virus (HDV). The latter virus consists of a protein
fragment called the delta antigen and a segment of RNA, and can only cause liver damage when
HBV is present.
 HDV requires the outside coat of HBV to infect cells. Therefore, one cannot become infected with
hepatitis D unless he or she already is infected with HBV.
 Chronic liver disease with cirrhosis is two to six times more likely in a co-infection.

3. Poxviridae
 Large and complex viruses that contains many enzymes
 Encode proteins that inhibit the host immune defense system
 Poxvirus infections are accompanied by a characteristic “rash”

Orthopoxviruses Description
Variola (Smallpox) starts with rashes that develops into lesions which are
abundant on the face, highly infective during the first week
of rash after the fever have begun and can be transmitted
by respiratory droplets and direct contact

Methisazone is a prophylactic drug


Cidofovir is effective in-vitro and in-vivo

Vaccinia (Cowpox) It was formerly used as a vaccine virus to protect against


smallpox. The vaccination caused a pustular exanthem
around the vaccination site, usually accompanied by fever
Monkeypox Causes human monkeypox infection discovered in the early
1970s in Africa, acquired by direct contact with wild animals
which are killed for food and skins
Cowpox acquired from cattle, causing human infections
characterized by hemorrhagic skin lesions
Buffalopox a derivative of vaccinia occuring in water buffalo, can cause
human infections characterized by localized pox lesions

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Parapoxviruses
ORF Virus - Causes contagious pustular dermatitis or sore
mouth
-Single lesion on a finger, hand or forearm but may
appear on the neck and face
-Occupational disease of sheep and goat handlers
transmitted by direct contact with infected animal

Molluscipoxviruses
Molluscum contagiosum virus -Causes molluscum contagiosum
-A benign epidermal tumor that occurs only in humans
(frequent in children); lesions are small, pink, wart-like
tumors on the face, arms, back and buttocks
-A sexually transmitted disease in young adults and
AIDS patients; itchy lesions

Yatapoxviruses
Tanapoxviruses - Causes tanapox infection
-A common skin infection in Africa acquired from
monkeys
Yaba Monkey Tumor Virus

4. Adenoviridae
 Usually attacks the epithelial cells of the eye, the respiratory, gastrointestinal and urinary tracts
 First Identified from the “Adenoidal Tissue” (tonsils)
Diseases:
4.1 Respiratory Diseases
 Acute RTI in young children (types 1, 2, 5, 6)
 Acute RTI in adolescents and adults (types 3, 4, 7)
 10 to 20% childhood pneumonia (type 3, 7, 21)
 Outbreak of severe respiratory disease in 2007 (type 14)
 Acute respiratory disease syndrome among military recruits (types 3, 4, 7)

4.2 Eye Infections


 “Swimming pool conjunctivitis” in children (types 3, 7)
 Epidemic and highly contagious keratoconjunctivitis in adults (types 8, 9, 37)

4.3 Gastrointestinal Diseases


 “Infantile gastroenteritis” a viral gastroenteritis in young children manifested as diarrhea (types
40 and 41)

4.4 Other Diseases


 Respiratory disease that progresses to severe and fatal pneumonia among transplant patients
(types 1 to 7)
 Acute hemorrhagic cystitis among young boys (types 11 and 21)

5. Papoviruses
Composed of three genera:
- Papillomaviruses
- Polyomaviruses
- Vacuolating viruses
NO LONGER exists because papillomavirus and polyomavirus are now classified under human cancer
viruses, vacuolating virus do not cause human infections

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Agents:
5.1 Human Papilloma Virus (HPV) – “Warts Viruses”

Agent Disease
HPV6, HPV11 Skin warts, plantar warts, flat warts, anogenital warts
laryngeal papillomas in children (recurrent
respiratory papillomatosis
HPV16, HPV18 Cervical Cancer
HPV16 Cancer of vulva, penis, anus, oropharyngeal

5.2 Human Polymoma Virus


Agent Disease
BK Virus causes hemorrhagic cystitis and polyomavirus-
associated nephropathy
JC Virus causes progressive multifocal leukoencephalopathy
KI and WU Viruses occurred in nasopharyngeal aspirates in children
with respiratory infections
Merkel Cell Virus associated with Merkel-cell carcinoma, a rare skin
tumor of neuroendocrine origin
;
6. Parvovirus
 Simplest DNA animal virus
 Only DNA virus that is single stranded
6.1 Parvovirus B19
 Pathogenic for humans and has a tropism for erythroid progenitor cells
Disease Description
Erythema Infectiosum “Fifth Disease” Children-Slapped-cheek Syndrome
Adult- Arthralgia and Arthritis
Transient Aplastic Anemia - Severe acute anemia
-Complication of underlying anemia such as in
patients with sickle-cell disease, thalassemias,
acquired hemolytic anemia and after bone marrow
transplants
Pure Red Cell Aplasia severe anemia in immunocompromised patients
Hydrops Fetalis -Viral infection on 2nd trimester of pregnancy
-Causes fatal death due to severe anemia that may
occur before the 20th week of pregnancy

RNA VIRUSES

RNA VIRUSES POSITIVE SENSE


Mnemonics: PiCoTCaFlaRe
– PicoRNAviridae
– Coronaviridae
– Togaviridae
– Caliciviridae
– Flaviviridae
– Retroviridae

General Characteristics of RNA Positive Sense Viruses


 All are icosahedral except CORONAVIRUS
 All are single stranded
 All are enveloped viruses except Picornaviridae, Caliciviridae
 All replicates in the cytoplasm except Retrovirus

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1. PicoRNAviridae
Pathogenic families
a. Enterovirus
b. Rhinovirus
1.1 Enterovirus - primarily infects the enteric tract and diffuses into different body parts

Poliovirus
 It enters in the mouth, multiplies in the oropharynx or intestines initially affects the peyer’s
patches of the intestines, then it diffuses to the motor neurons of the lower limbs
 Causes “Poliomyelitis” (polio = “gray”; myelo = for “spinal cord”), referring to the “gray matter,”
which is the nerve tissue of the spinal cord and brain in which the virus infects.
- Mild poliomyelitis – febrile illness
- Nonparalytic poliomyelitis – aseptic meningitis
- Paralytic poliomyelitis – flaccid paralysis

Prophylaxis:
Salk vaccine (JonasSalk) –a killed vaccine that induces humoral immunity but not local intestinal
immunity. Formaldehyde is used to inactivate the virus.
Mnemonics: salK - KILLED
Sabin vaccine (Albert Sabin) – a live attenuated virus grown in primary monkey or human diploid
cell cultures; produces IgM and IgG in the blood and in the intestines which provides resistance to
reinfection
Mnemonics: saBin - BUHAY

Coxsackie virus
 Named for the town “Coxsackie” in New York where they were first isolated
Groups of Coxsackie virus

Coxsackie group Diseases


Group A -Aseptic Meningitis (A7 and A9)
-Herpangina, a severe febrile vesicular
pharyngitis
-Hand, foot and mouth disease (A16) – oral and
pharyngeal ulcerations and a vesicular rash of the
palms and soles that may spread to the arms and
legs
Group B -Pleurodynia – “Bornholm disease” “Epidermic
myalgia” or “Devils grip” it is characterized by fever
and stabbing chest pain lasting for 2 days to 2
weeks

Group C

Echovirus
 ECHOvirus means “Entero Cytopathogenic Orphan Viruses”
 Infect the human enteric tract and can be recovered from humans only by inoculation of certain
tissue cultures
Diseases:
 Acute hemorrhagic conjunctivitis (Enterovirus 70)
 Meningitis, encephalitis, paralysis resembling poliomyelitis and hand-foot-and-mouth disease
(Enterovirus 71)

1.2 Rhinovirus
 Common colds virus”
 Transmitted through contaminated fingers – hand-to-hand, hand-to-eye, hand-to-
object-to-hand

1.3 Hepatovirus

Hepatitis A Virus
 Infectious Hepatitis
 Transmitted via Fecal-oral route

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2. Coronaviridae
 Helical Capsid Symmetry
 “Corona” refers to the permanent halo of spikes protruding from the envelope
 Cause of common colds, lower respiratory tract infections and gastroentritis in infants

SARS (Severe Acute Respiratory Syndrome) an emerging infectious disease of the lower
respiratory tract, was first reported in southeastern China in spring 2003, and quickly spread through
Southeast Asia and to 29 countries.

MERS-CoV (Middle East Respiratory Coronavirus) is a viral respiratory disease that was first
identified in Saudi Arabia in 2012. Although the majority of human cases of MERS have been attributed to
human-to-human infections, camels are likely to be a major reservoir for MERS-CoV and animal source of
MERS infection in humans.

3. Togaviridae

Two genera: Alphavirus and Rubivirus

Alphavirus - transmitted by arthropods and are imported to central Europe mainly by travelers to tropical
and subtropical countries.

Agent Vector Disease


Chikungunya Virus Aedes aegypti Infection that resembles dengue
Aedes albopictus
Western Equine Virus (WEV) Culex mosquito Encephalitis
Eastern Equine Virus (EEV) Culiseta mosquito Encephalitis
Venezuela Equine (VEE) Mosquito-borne Encephalitis

Rubivirus
 Causes Rubella (German Measles or 3-day Measles)
 An acute febrile illness characterized by a rash and lymphadenopathy affecting children and
young adults
 Mildest of common viral exanthems
 Rubella is dangerous to developing fetus in a pregnant woman, it can lead to Congenital Rubella
Syndrome
Triad of Congenital Rubella: Cardiac Anomalies, Cataract and Deafness
 Prevention: MMR Vaccine

4. Caliciviridae
 Naked virus
 Causes enteritis

Calicivirus
Norovirus Norwalk virus
Sapo virus Sapporo-like virus
Nebovirus Bovine enteric virus
Lagovirus Rabbit hemorrhagic disease virus
Vesivirus Vesicular exanthema virus

Norwalk virus
 It was named from an outbreak in Norwalk Elementary School in Ohio in 1969
 Causes outbreaks of gastroenteritis usually in settings such as schools, camps, cruise
ships and similar confined populations
 Associated with “winter vomiting disease”
 Transmitted by fecal-oral route
 Symptomatic treatment

Hepevirus
 Hepatitis E
- Enteric Hepatitis

- transmitted via fecal-oral route

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5. Flaviviridae

Genera: Flavivirus, Hepacivirus and Pestivirus

Flavivirus – transmitted by arthropods

Disease Vector
Yellow Fever Aedes aegypti Characterized by jaundice and
fever
Dengue Fever (Breakbone Female Aedes aegypti Influenza-like syndrome, severe
fever) Aedes albopictus muscle joint pains, nausea and
vomiting, eye pain and rash.
Associated with Dengue
Hemorrhagic Fever/Dengue
Shock Syndrome characterized
by thrombocytopenia,
hemorrhage and septic shock
St. Louis Encephalitis Culex mosquito Epidemic encephalitis
Reservoir: Wild birds (English
Sparrows)
West Nile Fever Culex mosquitoes Leading arboviral encephalitis in
US
Japanese B Encephalitis Culex mosquitoes Leading cause of viral
encephalitis in Asia
Zika Virus Aedes mosquitoes Fever, rash, joint pain and red
eyes
Tick-Borne Encephalitis Ixodes persulcatus and Ixodes important cause of encephalitis
ricinus in Europe, Russia and northern
China

Hepacivirus
 Hepatitis C
- Non A, Non B Hepatitis; Post transfusion hepatitis
- transmitted parenterally
- may lead to liver cancer

6. Retroviridae
 “Retro” pertains to the reverse transcriptase an RNA-directed DNA polymerase that can
transcribe ssRNA into double-stranded DNA.
 Cause tumors of the reticuloendothelial and hematopoietic systems (leukemia, lymphoma)
or of connective tissue (sarcoma)
 Includes Human T-Lymphotropic virus and Human Immunodeficiency virus
 Replicates in the Nucleus

Human T-Lymphotropic Virus (HTLV)


- Exists in Humans
- Tropism for matured T-cells

Diseases:
Adult T-cell leukemia lymphomas (ATL)
HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP),
characterized by progressive weakness of the legs and lower body

Human Immunodeficient Virus (HIV)


- Derived from a primate lentivirus common in Africa
- Includes HIV-1 and HIV-2
- Transmitted during sexual contact, parenteral exposure to contaminated blood or blood
products, and from mother to child during perinatal period
- Once infected individuals remain infected for life
- Tropism for CD4+ helper T-cells and macrophages that express CD4 on their surface

Diseases:
- HIV infections are nonspecific and manifestations include fatigue, rash, HA, nausea and
night sweats
- AIDS (Acquired Immunodeficiency Syndrome) is a pronounced suppression of the
immune system and development of opportunistic infections or unusual neoplasms

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RNA VIRUSES NEGATIVE SENSE

Mnemonics: Pairing Rats Fight Over Bunny

- Paramyxoviridae
- Rhabdoviridae
- Filoviridae
- Orthomyxoviridae
- Bunyaviridae
- Arenaviridae

General Characteristics of RNA Negative Sense Viruses


 Helical
 Single stranded
 Enveloped
 Replicates in Cytoplasm except Orthomyxoviruses

Mnemonics: HSEC

1. Paramyxoviridae - Major respiratory pathogens among infants and young children.

Includes:
– Respiratory syncytial virus
– Parainfluenza virus
– Mumps virus
– Measles virus

1.1 Respiratory syncytial virus


 Most important and the number one cause of pneumonia and bronchiolitis in infants and
young children
 Reinfection is common and appears as a common cold
 It can cause pneumonia, otitis media and recurrent episodes of wheezing illness

1.2 Parainfluenza virus


 3rd leading cause of LRTI and URTI in children and adults
 Rhinitis and pharyngitis
 Laryngotracheitis
 Croup (laryngotracheobronchitis)
 Bronchiolitis
 Pneumonia
 Most common complication is otitis media

1.3 Mumps virus


 An acute contagious
 disease characterized by nonsuppurative enlargement of one or both salivary glands
 Affects the parotid glands (parotitis) and prostate glands in males (orchitis)
 Prevention: MMR Vaccine

1.4 Measles Virus


 “Rubeola Virus”
 An acute, highly infectious disease characterized by fever, respiratory symptoms and a
maculopapular rash (Koplik spots) affecting the mouth, head, body and down the
extremities
 Complications associated: Symptomatic encephalitis, Subacute sclerosing
panencephalitis (SSPE) and Stillbirths
 Prevention: MMR Vaccine

1.5 Human Metapneumovirus


 A respiratory pathogen first described in 2001
 Can cause mild upper respiratory symptoms to severe lower respiratory symptoms among
patients who have negative test results for known respiratory viruses

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2. Rhabdoviridae
 A bullet-shaped virus that causes rabies
 An acute infection of the CNS that is almost always fatal
 Transmitted to humans from the bite of a rabid animal
 Reservoir: dogs, bats, raccoons, skunks and foxes

2.1 Rabies Virus


 Causes rabies an acute, fulminant and fatal encephalitis
 Negri bodies, round or oval inclusions within the cytoplasm of nerve cells of animals
infected with rabies

Phases of Rabies

Prodromal Phase
Usually lasts for 2 to 10 days showing symptoms of malaise, anorexia, HA, photophobia,
N and V, sore throat and fever, abnormal sensation in wound bite

Neurologic Phase
Lasts for 2 to 7 days showing CNS dysfunctions like nervousness, apprehension,
hallucinations and bizarre behaviors, general sympathetic activity, hydrophobia, aerophobia,
swallowing precipitates a painful spasm of the throat muscles

Coma Phase
Convulsive seizures, coma and death

Treatment:
Rabies vaccines
HDCV – Human Diploid Cell rabies Vaccine
PCEC – Purified Chick Embryo Cell vaccine
RVA – Rabies Vaccine Adsorbed
Antibodies
HRIG – Human Rabies Immunoglobulin
equine antirabies serum

3. Filoviridae
 “Filo” means “thread” and refers to their long filaments
 Highly virulent viruses causing hemorrhagic fevers that usually ends in death
 No known natural reservoir
 Have a tropism for cells of the macrophage system, dendritic cells, interstitial fibroblasts
and endothelial cells

3.1 Marburg Virus


 Causes hemorrhagic fever
 First recognized as a cause of human disease in 1967 in Germany and Yugoslavia (due
to exposure to African green monkeys “Cercopithecus aethiops” from Uganda)

3.2 Ebola Virus


 Named for the river in Zaire that was the site of outbreak of hemorrhagic fever in 1976
 Transmitted through contact with patients’ blood or secretions
 Causes severe disease in humans and in non-human primates
 Ebola Reston Virus, detected in 1989 from Cynomolgus monkeys (Macara fascicularis)
from the Philippines

4. Orthomyxoviridae
 “Myxo” refers to their affinity for mucins and “ortho“ is added to distinguished them from
the paramyxoviruses
 Spread through air-borne transmission → viruses deposit in lower respiratory tract, their
primary site is the tracheobronchial mucosa
 Repllcates in the nucleus
Includes:
- Influenza virus

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Two antigens:
HA (Hemagglutinin active antigen)
Necessary for viral absorption into the cell
Binds with sialic acid found in cellular membrane of RBC to initiate the infection
NA (Neuraminidase active antigen)
Hydrolyzes neuraminic acid, important component of mucin
Enhances the ability of the virus to infect the respiratory epithelium
A protein assisting in the release of the virions from the host cell when replication is
complete

Causes two types of antigenic changes


Antigenic shift
Major changes based on the reassortment of segments of its RNA, leads to pandemic
disease
Antigenic drift
Minor changes based on mutations on the RNA, leads to endemic disease

4.1 Influenza
Classic influenza (Types A and B)
Common cold illness (Type C)
Croup in children (Type A)
4.2 Pneumonia – a complication common in elderly, debilitated patients and pregnant women
4.3 Reye's syndrome – acute encephalopathy in children and adolescents (2 to 16 years of age);
a complication with types A and B and VZV, occurring after use of salicylates
4.4 Guillain Barre Syndrome - occurs when the body mistargets the infection and instead
damages its own peripheral nerve cells, causing muscle weakness and sometimes paralysis.

5. Bunyaviridae

Arthropod-borne
Agent Vector Diseases
California Encephaliris Virus Aedes triseriatus encephalitis and aseptic
“La Crosse Virus” meningitis in children
Sandfly Virus Phlebotomous papatasii Phlebotomous fever
Rift Valley Virus Aedes Rift Valley Fever
Pathogen for domestic
livestocks

Rodent-borne
Hantavirus
Has worldwide distribution causing two serious and often fatal human diseases:
1. Hemorrhagic fever with renal syndrome (HFRS) is an acute infection causing interstitial
nephritis that can lead to acute renal insufficiency and renal failure
 Transmitted by urban rats like Apodemus agrarius (in Korea)
 Viruses causing HFRS includes:
*Hantaan virus and Dobrava virus (Asia and Europe)
*Seoul virus (Eurasia)
2. Hantavirus pulmonary syndrome (HPS) is a disease that begins with fever, HA and myalgia
followed by rapidly progressing pulmonary edema that leads to a severe respiratory
compromise
*Sin Nombre virus (North America) whose rodent reservoir is the deer mouse,
Peromyscus maniculatus
*New York virus, Black Creek Canal virus, Bayou virus in US
*Andes virus in Argentina and Chile
*Choclo virus in Panama

6. Arenaviridae
 “Arena” means “sand” and refers to granules in the virion surface that are actually
nonfunctional ribosomes
 Establish chronic infections in rodents (species-specific)
 Human transmission is by contact with rodent excreta

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Agent Reservoir Disease
Lassa Virus Mastomys natalensis – “lassa fever” a severe and
1969- Nigerian Town of House rat fatal form of hemorrhagic
Lassa fever affecting multiple
DOC: Ribavirin organs
Junin Virus Calomys musculinus “Junin hemorrhagic fever” in
Argentina
Machupo Virus Calomys callosus “Machupo hemorrhagic
fever” in Bolivia
Guanarito Virus “Venezuelan hemorrhagic
fever”
Sabia Virus Fatal hemorrhagic fever in
Brazil

Double Stranded RNA Virus

1. REOviridae
 REO is an acronym for Respiratory, Enteric and Orphan
 It was isolated from respiratory and enteric tracts and was not associated with any disease
 The only double stranded RNA virus

Includes:
Rotavirus
Orbivirus
Coltivirus

1.1 Rotavirus
– Most common cause of infantile gastroenteritis
– The virus is transmitted by the fecal-oral route, where it infects and damages
the cells that line the small intestine
– Treatment and Prevention:
Supportive treatment
Oral vaccines

1.2 Orbivirus
– Commonly infects insects and can be transmitted to vertebrates
– No serious human disease, only mild fevers
– Examples:
Bluetongue virus of sheep
African horse sickness virus

1.3 Colorado Tick Fever Virus


– Causes colorado tick fever/mountain fever or tick fever → characterized by fever,
headache, retroorbital pain and severe myalgia
– Transmitted by wood tick Dermacentor andersoni among small rodents of the rocky
mountains like chipmunks and squirrels

Atypical Virus-Like Agents

PRIONS
 Prions consist of a cell-coded protein (PrP: prion protein) altered in its conformation and by point
mutations. They are infectious and can cause normal cellular PrP to assume the pathological
configuration.
 Human Prion Disease
Creutzfeldt-Jakob Disease (CJD)
Kuru
 Animal Prion Disease
Scrapie
Bovine Spongiform Encepalopathy (Mad Cow Disease)

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DEFECTIVE VIRUSES
 Composed of viral nucleic acid and proteins but cannot replicate without a helper virus, which
provides missing function
 Usually have a mutation or a deletion of part of their genetic material

PSEUDOVIRIONS
 Contain host cell DNA instead of viral DNA within the capsid
 Formed during infection with certain viruses when the host cell DNA is fragmented and pieces of
it are incorporated within the capsid protein
 Can infect cells but they do not replicate

VIROIDS
 Consist solely of a single molecule of circular RNA without a protein coat or envelope
 Cause several plant diseases but are not implicated in any human diseases

SUMMARY OF HEPATITIS VIRUSES

Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E


Family Picornaviridae Hepadnaviridae Flaviviridae Unclassified Caliciviridae
Genus Hepatovirus Orthohepadnavi Hepacivirus Deltavirus Hepevirus
rus
Genome ssRNA (+) dsDNA ssRNA (+) ssRNA ssRNA (+)
Transmission Fecal-oral Parenteral Parenteral Parenteral Fecal-oral
Other Name Infectious Serum hepatitis Non A, Non B hepatitis Enteric
hepatitis Post transfusion hepatitis Hepatitis

SUMMARY OF ARTHROPOD-BORNE VIRUSES

Agent Family Genus Genome


East Equine Encephalitis Virus Togaviridae Alphavirus RNA (+) sense
West Equine Encephalitis Virus Togaviridae Alphavirus RNA (+) sense
Chikungunya Virus Togaviridae Alphavirus RNA (+) sense
St. Louis Encephalitis Virus Flaviviridae Flavivirus RNA (+) sense
West Nile Fever Virus Flaviviridae Flavivirus RNA (+) sense
Japanese B Encephalitis Virus Flaviviridae Flavivirus RNA (+) sense
Tick-Borne Encephalitis Virus Flaviviridae Flavivirus RNA (+) sense
Yellow Fever Virus Flaviviridae Flavivirus RNA (+) sense
Dengue Virus Flaviviridae Flavivirus RNA (+) sense
Zika Virus Flaviviridae Flavivirus RNA (+) sense
California Encephalitis Virus Bunyaviridae Bunyavirus RNA (-) sense
Sandfly Virus Bunyaviridae Phlebovirus RNA (-) sense
Rift valley Virus Bunyaviridae Phlebovirus RNA (-) sense

SUMMARY OF RODENT-BORNE VIRUSES


Agent Family Genome
Hantavirus Bunyaviridae RNA (-) sense
Lassa virus Arenaviridae RNA (-) sense
Junin virus Arenaviridae RNA (-) sense
Machupo virus Arenaviridae RNA (-) sense
Guanarito virus Arenaviridae RNA (-) sense
Sabia virus Arenaviridae RNA (-) sense
LCM virus Arenaviridae RNA (-) sense
Marburg virus Filoviridae RNA (-) sense
Ebola virus Filoviridae RNA (-) sense

*For Human Cancer Viruses, refer to table 43-1 of Jawetz p. 620 

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SUMMARY OF ANTI-FUNGAL AGENTS
Anti-Herpes Agents

Drug MOA Example


Acyclovir Base analog (mimics guanine) Genital herpes, chicken pox,
inhibiting DNA replication shingles
Ganciclovir Base analog (mimics guanine) CMV Retinitis
inhibiting DNA replication
Vidarabine Terminates DNA elongation Shingles and herpesvirus-caused
encephalitis
Idoxuridine Base analog (thymidine) causing Keratitis caused by herpesvirus
Trifluridine replication errors mutations infection
Foscarnet Inhibits DNA polymerase Retinitis caused by Herpesvirus
infection

Anti-Retroviral therapy
a. Nucleoside reverse transcriptase inhibitors (NRTI)
Mnemonics: DAZZLEST

Didanosine
Abacavir
Zidovudine (AZT)
Zalcitabine
Lamivudine
Emtricitabine
Stavudine
Tenofovir

b. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)


Mnemonics: “vir” at the middle.

Delavirdine
Efavirenz
Etravirine
Nevirapine

c. Protease inhibitors - react with the HIV protease, the enzyme that trims viral proteins down to
working size for the construction of the capsid
Mnemonics: “vir” at the end

Atazanavir
Darunavir
Fosamprenavir
Indinavir
Lopinavir
Ritonavir

a. Entry Inhibitor
Enfurvirtide – blocks penetration/uncoating
Maraviroc – Blocks attachment or penetration

b. Integrase Inhibitor

Raltegravir

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Anti-Hepatitis Agents

a. Interferon alfa
– Appears to function by induction of intracellular signals following binding to specific cell
membrane receptors, resulting in inhibition of viral penetration, translation, transcription,
protein processing, maturation, and release, as well as increased host expression of major
histocompatibility complex antigens, enhanced phagocytic activity of macrophages, and
augmentation of the proliferation and survival of cytotoxic T cells.

b. Lamivudine
– Hepatitis B
– Inhibits HBV DNA polymerase

c. Ribavirin
– Base analog (mimics guanine) inhibiting viral replication
– Hepatitis C

Anti-Influenza Agents
Drug MOA Example
Amantadine Blocks viral uncoating Influenza A
Rimantadine Blocks viral uncoating Influenza A
Oseltamivir (Tamiflu) Neuraminidase inhibitors (viral Influenza A
release)
Zanamivir Neuraminidase inhibitors (viral Influenza A
release)

=== END ===

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