Diseases Caused by Viruses

1. Basic Terminology
Pathogens: Any organism that causes disease. There are plant pathogens, animal
pathogens, and fish pathogens, as well as the subject of this book, human pathogens.
Host: A larger organism that supports the survival and growth of a smaller organism.
Virulence: Degree of potency of the pathogens.
Epidemiology: the “who, what, when, and where” of infectious diseases.
Pathogenicity: Ability of a pathogen to cause a disease.
Opportunistic pathogen: Such an organism; it infects a host away from its
typical niche, especially in a host with a weakened immune system (a compromised host).
Reservoir: The natural environmental location in which the pathogen normally resides. For
Example: birds as reservoir of West Nile virus and contaminated drinking water as the reservoir of
Vibrio cholerae.

2. Infectious disease: Disease that results from antagonism with microbial agents
such as viruses, bacteria, fungi, and protozoa. When a pathogen is growing and multiplying within
or on a host, the host is said to have an infection. An infection may or may not result in overt
disease.
The Chain of Infection: The infectious disease process requires that a specific
agent of substantial virulence is exposed to a susceptible host in an appropriate dose (number of
organisms). All links of the chain are necessary for infectious disease to result. Breaking the chain,
by removal of any link, prevents infectious disease.

3. Overview of the Infection Process: The infectious disease process is
complex and dynamic. To the host, infection is at best an annoyance and at worst lethal, if the
microorganism succeeds. To microorganisms, infection is focused on finding a suitable environment,
obtaining nutrients, and avoiding host immune responses to establish a niche. Microorganisms use
numerous physical and chemical strategies to survive.

4. Pathogenesis: When a potential pathogen reaches its host, the features of the organism
determine whether or not disease ensues. The primary reason pathogens are so few in relation to
the microbial world is that being successful at producing disease is a very complicated process.
Multiple features, called virulence factors, are required to persist, cause disease, and escape to
repeat the cycle. The variations are many, but the mechanisms used by many pathogens have now
been dissected at the molecular level.
Source: The source can be either animate (e.g., humans or animals) or inanimate (e.g., water
or food).
Period of infectivity: The time during which the source—such as a human, or
contaminated water—is disseminating the pathogen.
Zoonoses: Infectious diseases that can be transmitted from animals to humans.
Virulence: The magnitude of harm (pathogenicity) caused.
Virulence factors: Any structural or soluble product that increases pathogenicity.
Virulence factors enable the microbe to counter the challenges of the host environment.

5. Transmission of Infectious Disease: Infectious diseases can be
transmitted by various direct and indirect methods.

6. Toxin: A substance that alters the normal metabolism of host cells with deleterious effects on
the host. Toxigenicity is the pathogen’s ability to produce toxins.
Toxaemia: Condition when toxins have entered the blood of the host.
Intoxications: Diseases that result from a specific toxin (e.g., botulinum toxin, tetanus
toxin) produced by the pathogen.
Phases of an Infectious Disease:
1. Incubation Period: The time between pathogen entry and the development of signs and
symptoms. The pathogen is reproducing but has not reached a sufficient level to cause clinical
manifestations. This period’s length varies with the disease.
2. Prodromal stage: It occurs with an onset of signs and symptoms that are not yet specific
enough to make a clear diagnosis. However, the patient often is contagious. This is followed
by the illness period when the disease is most severe and displays characteristic signs and
symptoms. The host immune response is typically triggered at this stage.
3. Recovery stage (convalescence): the period of decline, the signs and symptoms begin to
disappear.

7. Infectious dose 50 (ID50): The inocula can be measured experimentally to
determine the number of microorganisms required to cause disease in 50% of the inoculated hosts.
Lethal dose 50 (LD50): The experimental determination of the number of
microorganisms required to be lethal to a host species.
Extracellular pathogens: Infectious microorganisms that during the course of
the disease, they remain in tissues and fluids but never enter host cells.
Intracellular pathogens: Microbes that grow and multiply within host cells.
Pathogenicity Islands: Large segments (10 to 200 kilobases) of bacterial
chromosomal and plasmid DNA have been found to encode virulence factors.
Tropism: The ability of a given pathogen to infect a specific location like organ, tissue or cell.

8. Viral Diseases
Viral diseases are infections caused
by viruses. Different types of viruses
cause different infections. Common
viral illnesses include colds, the flu,
COVID-19, norovirus (“stomach
flu”), HPV (warts) and herpes
simplex virus (cold sores). Many
viruses go away on their own, but
some cause life-threatening or
chronic illnesses.
Virus replication cycle: A general scheme of the six
discrete steps of virus replication cycle, including
attachment, penetration, uncoating, synthetic phase
(transcription, translation and replication), assembly, and
release.

9. Viral pathogenesis comprises of several
stages, including:
● transmission and entry into the host,
● spread in the host,
● tropism,
● virulence and cytopathogenicity,
● patterns of viral infection and disease,
● host factors,
● host defense, and
● virus-induced immunopathology
Viruses are transmitted via:
● horizontal (person to person),
● vertical (mother-to-child) routes
● vector (from mosquitoes, animals).
Viral Diseases

10. Three major outcomes can be attributed to a viral infection:
(1) abortive infection, in which no progeny virus particles are produced, but the cell
may die because early viral functions can occur;
(2) lytic infection, in which active virus production is followed by cell death;
(3) persistent infection, in which small numbers of virus particles are produced with
little or no CPE (cytopathic effects).
Persistent infections include
● latent infection, in which viral genetic material remains in host cell without
production of virus and may be activated at a later time to produce virus and/or
transform the host cell;
● chronic infection, which involves low level of virus production with little or no CPE.
● viral transformation, in which viral infection or viral gene product induces
unregulated cellular growth, and cells form tumors in the host.
If two closely related viruses infect a host, then infection by the first virus can
inhibit the function of the second virus; this is termed interference.
Viral Diseases

11. Routes and sites of entry of viruses into hosts including food and water, aerosol, respiratory,
gastrointestinal, break in the skin, via mucosal or blood, insect or animal bite, and urogenital, anal or
sexual routes.

12. Summary of methods used to diagnose viral infections.

13. General scheme of antiviral action

14. Disease
Caused
by
Transmissi
on
Incubati
on
Period
Symptoms
Severity
and/or
complications
Antivir
al Drug
and
Vaccine
Chickenpox
(Varicella)
ds DNA
varicella-
zoster virus
Droplet
inhalation into
the respiratory
system
10 to 23
days
Small vesicles erupt
on the face or upper
trunk, fill with pus,
rupture, covered by
scabs
Reactivated in
immunocompromise
d persons and cause
sensory nerve
damage and
Shingles
Acyclovir.
MMVR
vaccine
Influenza
Influenza
Virus
Aerosol
droplet
inhalation into
the respiratory
system
1 to 2 days
Fever, cough
(usually dry),
headache, muscle
and joint pain,
severe malaise, sore
throat, runny nose
Inflammation of the
heart (myocarditis),
brain (encephalitis)
or muscle tissues
(myositis,), and
multi-organ failure
Peramivir
Zanamivir,
Tamiflu
Baloxavir
marboxil
Measles
Measles
virus
Respiratory
tract or the
conjunctiva
of the eyes
10 to 14
days
Nasal discharge,
cough, fever,
headache, and
conjunctivitis
Subacute sclerosing
panencephalitis:
progressive
degeneration of the
CNS
No
treatment,
MMR
vaccine

15. Disease
Cause
d by
Transmission
Incuba
tion
Period
Symptoms
Severity and/or
complications
Antivir
al Drug
and
Vaccine
Mumps
Mumps
virus
Saliva and respiratory
droplets
16 to 18
days
Swelling
and tenderness of
the salivary
(parotid) glands
Deafness, meningitis,
encephalitis,inflammat
ion of the epididymis
and testes (orchitis)
leading to sterility
Therapy,
MMR
vaccine
Rubella
Rubella
virus
Respiratory tract
12 to 23
days
Rash of small red
spots and light
fever.
Congenital rubella
syndrome
MMR
vaccine
Smallpox
Variola
virus
Respiratory tract,
infected
bodily fluids or
contaminated objects
12 to 14
days
Prodrome of
systemic aches,
fever, rash: firm,
deep- seated
vesicles/ pustules
Death is due to
toxemia associated
with immune-
mediated blood clots
and elevated BP
Smallpox
vaccine
Rabies
Rabies
virus
Direct contact with
saliva or brain/nervous
system tissue from
infected animal
10-365
days
Avg: 20-
90 days
Weakness, fever,
headache, tingling
at the site of bite
Coma, hallucination,
hydrophobia,
Paralysis,
Hyperactivity, Death
Rabies
Vaccine

16. Disease
Caused
by
Transmissi
on
Incubati
on
Period
Symptoms
Severity and/or
complications
Antivira
l Drug
and
Vaccine
Chikungun
ya
Chikungun
ya virus
Aedes aegypti
and Aedes
albopictus
mosquitoes.
3 to 7 days
Fever and joint
pain, headache,
muscle pain,
joint swelling,
or rash
Prolonged joint pain, eye
inflammation,
myocarditis, hepatitis,
nephritis, hemorrhage,
encephalitis, and
Guillain-Barré syndrome.
No
vaccine, no
treatment,
insect
repellant
Dengue
Dengue
virus)
Aedes aegypti
or Aedes
albopictus
mosquito
5–7 days
(range,
3–10 days)
high fever, an
erythematous
rash, and severe
pain in the back,
head, eyes
(behind eyes),
muscles, bone
and joints
Nose or gum bleed,
petechiae, or bruising,
shock, pleural effusion,
severe abdominal pain
and vomiting, and
hemorrhage often
followed by death.
Dengvaxia
®
(CYD-TDV)
Polio Polio virus
fecal-oral
route, food and
water
6 to 20
days
fever, headache,
sore throat,
vomiting, loss of
appetite.
Motor and muscle
paralysis
pocapavir
(V-073),IP
V

17. AIDS (HIV)
● AIDS is the result of an infection by the human
immunodeficiency virus (HIV), a positive-strand, enveloped
RNA virus within the family Retroviridae.
● HIV is acquired and may be passed from one person to
another when infected blood, semen, or vaginal secretions
come in contact with an uninfected person’s broken skin
or mucous membranes.
● HIV can remain clinically latent in most infected patients,
but when allowed to replicate in the absence of effective
immune response and other factors, high levels of virus
are produced causing CD4+
T-lymphocyte cell death and
AIDS.
● Gp120 binds to CD4 receptor and coreceptor and CCR5 or
CXCR4 (chemokine receptor) binds on CD4+ T-cells and
other cells.

18. HIV Life Cycle

19. ● The integrated provirus can remain latent, giving no
clinical sign of its presence. Alternatively the provirus
can force the cell to synthesize viral mRNA
● Once a person becomes infected with HIV, the course
of disease may vary greatly. The acute infection
stage occurs 2 to 8 weeks after HIV infection, referred
to as acute retroviral syndrome, with symptoms that
may include fever, malaise, headache, macular (small,
red, spotty) rash, weight loss, lymph node
enlargement (lymphadenopathy), and oral candidiasis.
● During this stage, the virus multiplies rapidly and
disseminates to lymphoid tissues throughout the
body, until an acquired immune response (antibodies
and cytotoxic T cells) can be generated. Because
these T-helper cells are critically important in the
generation of acquired immunity, individuals at this
stage develop a variety of symptoms.

20. ● As CD4+ T-cell numbers continue to decline, some patients develop opportunistic infections, such
as oral candidiasis (thrush), tuberculosis, and infections rarely seen in other patients, including
Mycobacterium avium complex (MAC), cryptococcal pneumonia, cytomegalovirus (CMV) infections,
acute toxoplasmosis, or Pneumocystis pneumonia (PCP).
● In addition to its devastating effects on the immune system, HIV infection can also lead to disease of
the central nervous system when virus-infected macrophages cross the blood-brain barrier.
● The classical symptoms of central nervous system disease in AIDS patients are headaches, fevers,
subtle cognitive changes, abnormal reflexes, and ataxia (irregularity of muscular action). Dementia
and severe sensory and motor changes characterize more advanced stages of the disease.
● Individuals infected with HIV-1 have an increased risk of three types of tumors:
○ the human herpesvirus 8–induced Kaposi’s sarcoma,
○ carcinomas of the mouth and rectum,
○ B-cell lymphomas or lymphoproliferative disorders.
Stage 2: Clinical Latency or Chronic Phase. The initial infection is followed by an asymptomatic period
(clinical latency) that can continue for years before the disease becomes clinically apparent. More than
60% of infected individuals remain in clinical latency for about 10 years after infection before they develop
significant disease, and the number continues to increase thereafter if untreated.

21. Temporal changes in viral load, anti-HIV-1
immune responses, and total CD4 T-cell counts
during various stages of HIV-1 infection.

22. Treatment

23. Diagnosis: Laboratory diagnosis of HIV infection can
be by isolation and culture of the virus or by using
assays for viral reverse transcriptase activity or viral
antigens. However, diagnosis can be accomplished
through the detection of specific anti-HIV antibodies
in the blood. A number of newer antibody- based
rapid tests have decreased reports of false results.
The most sensitive HIV assay employs the PCR, that
amplifies and detects tiny amounts of viral RNA and
proviral DNA in infected host cells. Quantitative PCR
assays provide an estimate of a patient’s viral load.
Prevention: Understanding risk factors and
practicing strategies to reduce risk are essential in
the fight against AIDS. Barrier protection from blood
and body fluids greatly limits risk of HIV infection.
Education to prevent the sharing of intravenous
needles and syringes is also very important.
Additionally, prevention includes the continued
screening of blood and blood products.