RNA

VIRUSES

Department of Microbiology
Universitas Brawijaya
2019
Brooks GF et al, 2013. Jawetz & Melnick Medical Microbiology. McGraw Hill Companies.
Picornaviridae
• Enterovirus
• Poliovirus
• Coxsackieviruses
• Echoviruses
• Rhinovirus
Retroviridae
• HIV

Hepatitis (RNA) Virus

• Hepatitis A, C, D, E
Picornaviridae
ssRNA, (+) sense
Unenveloped, icosahedral
Contains 12 genera

• Infect human & lower animals, causing various

illnesses ranging from poliomyelitis to aseptic
meningitis to the common cold.
• Enteroviruses are stable at acid pH (3.0–5.0) for
1–3 hours, rhinoviruses are acid labile

Enterovirus Rhinovirus

• Isolated from feces • Cannot be isolated from

• Poliovirus, Coxsackievirus, feces
Echovirus • Acid labile
• Acid stable
Picornavirus: Proteins
• Surface protein
• Antibody binding site
• VP 1 and VP 3
• Internal protein
• Linked with chord to RNA
• VP 4
 Poliovirus
• Poliovirus particles are typical enteroviruses
• Inactivated by a chlorine, not affected by ether or sodium
deoxycholate
• Restricted host, may infect human and other primates
(monkeys and Chimpanzees)
• long-term excretion of poliovirus has been observed in
some immunodeficient persons

• The etiology of poliomyelitis, which commonly presents as

flaccid paralysis
• There are three antigenic types of polioviruses.
 Poliovirus

Epidemiology
• Prevaccine era : endemic, pandemic
• Vaccine era  global eradication effort
• Children are more susceptible than adults
• Developing countries : infantil paralysis (in infant)
• Developed countries : shifted age of incidence to
toddler
 Poliovirus
incubation period: 7 -
14 days (3 – 35 days) Pathogenesis

B. Blondel, T. Couderc, F. Delpeyroux. Enteroviruses in Encyclopedia of the Neurological Sciences (Second Edition), 2014.

Poliovirus: Clinical Finding
A. Abortive poliomyelitis
(Mild disease)
the most common form of
the disease
minor illnes: fever, malaise,
nausea, vomiting, headache,
constipation, drowsiness, sore
throat (in various combination)
patient recovers in a few
days
Poliovirus
B. Non paralytic
poliomyelitis
(aseptic meningitis)
symptoms & sign as above,
but with stiffness + pain in
back & neck for 2 – 10 days
  fast healing and
complete
 Poliovirus

Poliovirus: Clinical Finding

D. Progressive
C. Paralytic poliomyelitis postpoliomyelitis muscle
atrophy
flaccid paralysis 
unilateral
( cause of lower motor a result of physiologic
neuron damage ) and aging changes in
paralytic patients
already burdened by loss
healing 6 months, with of neuromuscular
residual paralysis lasting functions
much longer
 Poliovirus

Laboratory diagnosis
• Sample : throat swabs taken soon after
onset of illness and from rectal swabs or stool samples
collected over long periods
• Nucleic acid detection: PCR
• Viral Isolation :
• Culture : CPE appear in 3-6 days
• Neutralization
• Serology :
• Paired serum to show a rise of antibody titer
 Poliovirus

Immunity
• immunity is permanent against the virus type
causing the infection, antibody mediated
• Maternal antibodies gradually dissapear during first
6 months.
• Passive antibody : 3-5 weeks.
• Poliovaccine:
• salk (killed virus) vaccine
• sabin (live attenuated virus) vaccine
 Poliovirus

Poliovirus: Salk Vaccine

• Derived from PMK cell culture

Does not inhibit

Induces humoral
Administered poliovirus from
immunity but not
intravenous entering intestinal
intestinal immunity
mucous membrane
 Poliovirus

Poliovirus: Sabin Vaccine

• Derived from PMK and human
diploid cells

Infectious
The live
Stimulate progeny of the
poliovaccine
Administered humoral & vaccine virus are
multiplies &
orally intestinal disseminated in
infects intestinal
immunity the community
tract
 herd immunity

•may mutate  paralytic disease

•interference by another enterovirus
BEFORE POLIO VACCINE: SNAPSHOTS OF LIFE IN THE SHADOW
OF POLIO

http://polioeradication.org/news-post/before-polio-vaccine-snapshots-of-life-in-the-shadow-of-polio/
http://www.npr.org/sections/health-shots/2012/10/16/162670836/wiping-out-polio-how-the-u-s-snuffed-out-a-killer
Polyomyelitis cases in United States
Poliovirus

Poliomyelitis -
United States,
1950-2011

Wild polio virus

1988 2012
https://www.cdc.gov/vaccines/pubs/pinkbook/images/polio-fig-02.jpg
Coxsackievirus

• Overview
• Pathogenesis
• Clinical Finding
 Coxsackie virus
• Isolated in 1948 at Coxsackie, New York
• Divided into 2 groups, Group A and B (now
classified as Human Enterovirus (HEV) groups A,
B, C.
based on:
- cytopathic effect
- immunologic characterization
- pathogenicity
• Diagnosis is made similarly as other enterovirus
• Currently there is no vaccine / antiviral available
 Coxsackievirus

Coxsackie: Overview

Group A: Group B:

• myositis • pancreatitis,
• flaccid paralysis myocarditis,
• 23 serotypes encephalitis,
hepatitis
• irregular muscle
tonicity
• 6 serotypes
 Coxsackievirus

Coxsackie: Pathogenesis
Transmission:
direct contact, droplets or fecal-oral

Virus Causes various

Incubation: 2 – distribution = manifestation,
9 days enterovirus; in generally
throat and feces subclinical

Clinical
manifestation
depends on
group
 Coxsackievirus
Coxsackie: Clinical Findings
variety of illness
neurologic: aseptic skin & mucosa: cardiac & muscular:
meningitis, herpangina , hand- pleurodynia,
meningoencephalitis, foot & mouth disease myocarditis,
paralysis (HFMD) pericarditis

ocular: acute resp. infection:

gastrointestinal:
conjunctivitis common cold ,
diarrhea, hepatitis
hemorrhage pneumonia

other: e.g.
Undifferentiated
febrile illness,
diabetes mellitus
 Coxsackievirus

Coxsackie: Clinical Findings

• Coxsackie-vi is related to type-1 Diabetes Mellitus
(virus type B3 and B4)

Molecular mimicry hypothesis:

• Aequence AA's equality on Coxsackie B by glutamic
acid decarboxylase (enzyme of cell- β Pancreas )
known to be targets of autoimmunity in type 1
diabetes mellitus
HAND FOOT AND MOUTH DISEASE (HFMD) Coxsackievirus

HERPANGINA (vesicular pharyngitis)

https://redbook.solutions.aap.org/chapter.aspx?sectionid=8
8187140&bookid=1484

https://microbewiki.kenyon.edu/index.php/Coxsackievirus_A16

https://www.cdc.gov/mmwr/volumes/65/wr/mm6526a3
.htm
 Coxsackievirus

Laboratory Diagnosis
• Recovery of Virus
• Specimen: throat washing, stools, nasal secretions, CSF,
conjunctival swabs
• Inoculation on Tissue culture / suckling mice
• Nucleic acid detection : PCR / Real-time PCR
• Serology
• Neutralizing Ab
Other Enterovirus
• Echovirus : Enteric Cytopathic Human Orphan
• Infect human GI tract
• Recovered from human only by inoculation of certain tissue
cultures
• Found during trial period of polio vaccination
• There are > 30 serotypes
• Diseases:
• Aseptic meningitis
• Encephalitis
• Febrile illness with / without rash (rash usually found in children)
• Common cold
• Ocular disease
• Infantile diarrhea
Rhinovirus: Overview
• Causes common cold, commonly isolated from
nose / throat of mildly respiratory infection
patients
• Associated with majority of acute asthma
exacerbation
• There are > 150 serotypes
• Hosts: human, gibbon, chimpanzee
• No specific therapy is needed when infected.
Antimicrobial tx may be needed to prevent
secondary bacterial infection
 Rhinovirus

Rhinovirus: Overview
• Bacterial secondary infection commonly occurs in
children  may progress to acute otitis media,
sinusitis, bronchitis or pneumonia  antibody is
found in serum and discharge
• Transmisson via direct contact, hand to hand or
hand to object
• Rhinovirus lives on contaminated surface for
several hours
 Rhinovirus

Rhinovirus: Pathogenesis
Incubation: 2 -4 days,
Acute symptoms: about 7 days (sneezing,
nasal obstruction, sore throat, mild
cough)

Replication in Increasing nasal

Entry via surface mucosa secret quantity
respiratory tract of nose and protein
epithelial cells concentration
Retrovirus
ssRNA, (+) sense
Icosahedral, enveloped
Has reverse transcriptase enzyme

Human Immunodeficiency Virus, Causes acquired

immunodeficiency syndrome (AIDS)
• Envelope consists of lipid and glycoprotein (gp 120
and gp 41)
• Inactivated by:
• Ethanol
• Glutaraldehyde
• Phenolic compound
• Sodium hypochlorite
• Heat (56oC for 10 minutes)
Attacks host cells which express CD4 molecules (i.e. T
lymphocyte, macrophage, dendritic cells)
 HIV

HIV: Pathogenesis

gp14 facilitates
membrane fusion
Attacking cells
Virus enters the between virion
with CD4 (receptor
body and cells (with
of gp120)
coreceptor CCR5 &
CXCR4)

RNA genome
Provirus integrates undergoes reverse Virus enters cell
to cell’s genome transcription to host
provirus
 HIV

HIV: Pathogenesis
• The production of mature and infectious viral
particles starts after several of the viral genes are
expressed as protein and the cells will lysis.
• Infection by HIV will cause alteration the function
of innate and adaptive immunity, since cell with
CD4 plays important role in both innate and
adaptive immunity.
• Clinically, 20% of cases  acute manifestations:
fever, lymphadenopathy, skin rash, cephalalgia.
 HIV

HIV: Pathogenesis
• ARC = AIDS related complex: persistent fever, night
sweat, chronic diarrhea, decrease of body weight,
general lymphadenopathies.
• Latent phase and ARC may happen for years.
• Full-blown AIDS is marked by opportunistic
infection and malignancy – Kaposy sarcoma.
 HIV

HIV: Pathogenesis
• Exact mechanism of immunosuppression caused by
HIV infection remains unclear, but some factors
need to be considered:
Infected Th cells is
Cell
The cells is directly vulnerable to
death/apopotosis I
killed by virus immune attack by
induced by virus
healthy T cells

T cells
replenishment is Defects in antigen Presence of
impaired by damage presentation immuno-
to the thymus and associated with suppressive virus-
lymph nodes and by infection of coded molecules
infections of stem dendritic cells (gp 120, gp 41)
cells
 HIV

AIDS:
Opportunistic Infection
1. Protozoa: T. gondii, Isospora belli,
Cryptosporidium
2. Fungi: Pneumocystis jiroveci, C.albicans,
C.neoformans
3. Bacteria: M.avium-intracellulare complex, M.
tbc, Salmonella sp, L.monocytogenes,
Streptococcus sp
4. Virus: CMV, HSV, VZV, HBV, Adenovirus,
Papovavirus,
 HIV

HIV: Transmission
• Transmission
• Direct-sexual contact
• Blood and body fluids
• Contaminated needles
• Vertical: from infected mother to offspring
• High-risk groups
Homosexual persons
Multiple sexual partners
Drug abusers - injection
Repeated transfusions
 HIV

HIV: Laboratory Diagnosis

• Detection of viral components –viral load
• Serology: ELISA, IF, Western blot
• Immunology: peripheral blood, lymphocyte
count ( TCD4 : TCD8 ratio), TCD4 count, tuberculin
test, immuno-globulin assay
• Isolation and identification of oppor-tunistic
infectious agents
 HIV

HIV-AIDS: Therapy
Against virus  ARV
(antiretroviral) drugs: Immunomodulator:
interferon, levamisol
• nucleosid inhibitor reverse
transcriptase: zidovudin
(AZT), lamivudin, stavudin
• non-nucleosid inhibitor Against opportunistic
reverse transcriptase: infection: appropriate
nevirapin, delavirdin antimicrobial agents
• protease inhibitor:
indinavir, saquinavir,
nelfinavir Supportive therapy:
• These drugs should be given nutrition,
in combination psychotherapy, etc.
 HIV

HIV-AIDS: Prevention
• Theoretically  vaccine, but some problems
remain:
• No animal hosts
• High mutation rate of virus
• Several portal of entry
• Health education, include safe sex education
• Donor selection
 HIV

The man who was immune to HIV

Man Immune To HIV Helped Scientists Fight

Virus.

Stephen Crohn, a New York artist and editor,

carried a genetic mutation that protected him
against HIV. He died last month at age 66. The
cause was suicide.
 HIV
The Berlin Patient

A HIV patient with Acute myeloid Leukemia (AML) who in 2007

underwent stem cell transplantation from an unrelated donor who
screened positive for the homozygous CCR5∆32 mutation.
The outcome was ultimately a success. Nearly eight years after his
transplant, Brown remains free of both his cancer and readily
detectable HIV.
http://defeathiv.org/berlin/
 HIV
HIV di Indonesia

Laporan Perkembangan HIV-AIDS & Penyakit

Infeksi Menular Seksual (PIMS) triwulan IV
tahun 2016. Ditjen P2P Kemenkes RI. 2016
 Hepatitis Hepatitis A, C, D, E

(RNA) Virus ssRNA

• Hepatitis A virus is part of Picornaviridae

• Hepatitis C virus is part of Flaviviridae
• Hepatitis E virus is part of Hepeviridae
• Hepatitis D is defective virus that can only infect
people which is being infected by Hepatitis B virus
in active state
• All hepatitis virus infection presents with jaundice,
which is caused by disturbance of liver function
HEPATITIS VIRUS

Hepatitis A Virus (HAV)

• Icosahedral virus with no envelope, stable in acidic
environment and resists heating.
• Transmitted via fecal and oral, infection occurs as
acute infection, never become chronic and only
seldom presents as fulminant state.
• HAV infection rarely shows cytopathic effect.
• May contaminate food, and since it is easily
transmitted between people, it may cause
outbreak.
HEPATITIS VIRUS

Hepatitis A Virus (HAV)

HEPATITIS VIRUS

Hepatitis C Virus (HCV)

• Positive ss-RNA virus.
• Spherical virus with envelope, unstable in presence
of ether and acidic environment.
• Transmitted via parenteral contamination.
• Commonly causes
• chronic infection (70-90%),
• progresses into chronic active hepatitis and
cirrhosis (10-20%)
• also oncogenic changes in hepatocyte 
hepatocarcinoma.
HEPATITIS VIRUS

Hepatitis C Virus (HCV)

HEPATITIS VIRUS

Hepatitis C Virus (HCV)

• HCV shows high genomic diversity between one
place to another throughout the world. Each part
of the worlf has its own predominating genotype.
• This diversity does not differ the clinical
manifestation it causes, but it makes difference in
response to antiviral therapy.
• HCV undergoes sequence variation throughout
chronic infection  thus it is hard to make vaccine
against HCV
HEPATITIS VIRUS

Hepatitis D Virus (HDV)

• Also known as delta-Ag (delta antigen), a negative

ss-RNA. The RNA only codes the delta-Ag.
• It is a defective virus and cannot infect host without
HBV infection.
• When in blood circulation, this virus uses HBsAg
envelope to facilitate infection.
HEPATITIS VIRUS

Hepatitis D Virus (HDV)

HEPATITIS VIRUS

Hepatitis E Virus (HEV)

• Like HAV, HEV is transmitted via fecal oral when

food or water is contaminated.
• Caused outbreak in New Delhi in 1955, and Kashmir
in 1978, causing at least 1700 death cases.
• Pregnant woman has 20% higher chance to suffer
from fulminant HEV infection.
• Has several functional enzyme inside virion,
including reverse transcriptase
• Animal has its own strain of HEV and there is
probability of HEV-spreading between human and
animal.
HEPATITIS VIRUS

Hepatitis E Virus (HEV)

HEPATITIS VIRUS

Hepatitis Virus Particles

Brooks et al., 2012

References
• https://www.cdc.gov/vaccines/pubs/pinkbook/poli
o.html
• Brooks GF et al, 2013. Jawetz & Melnick Medical
Microbiology. McGraw Hill Companies.
Thank you