Noakhali Science and Technology University

Department of Microbiology

Assignment on

“Slow virus infection”

Course Title: Virology

Course Code: MBG 3203

Submitted By Submitted To

Name: Sunjida Masud Mohammad Sharif Uddin

Roll: BFH2005017F Assistant Professor
Session: 2019-20 Department of Microbiology
Year: 03, Term: 02 Noakhali Science & Technology University

Date of submission: 13 -01-2024

 Slow virus infection
A slow virus is a virus, or a virus like agent, etiologically associated with a slow virus disease. A slow virus
disease is a disease that, after an extended period of latency, follows a slow, progressive course
spanning months to years, frequently involves the central nervous system, and in most cases progresses
to death. Examples of slow virus diseases include HIV/AIDS, caused by the HIV virus subacute sclerosing
panencephalitis, the rare result of a measles virus infection and Paget's disease of bone (osteitis
deformans), which may be associated with paramyxoviruses, especially the measles virus and the
human respiratory syncytial virus.Two distinct groups cause serious degenerative diseases of the brain
and spinal cord. The first to be identified are those caused by "unconventional agents," kuru and
Creutzfeldt-Jakob disease. The second category, "conventional virus diseases," include SSPE (subacute
sclerosing panencephalitis), PML (progressive multifocal leukoencephalopathy), progressive rubella
encephalitis, and HIV encephalopathy. The universal focus on acquired immune deficiency syndrome
(AIDS) has stimulated new research on slow viruses.

Slow viruses produce diseases whose incubation periods range from several months to many years.
Because of this long latency period, the lack of inflammation produced by these diseases and the lack of
recoverable virus particles, it is only recently that the association has been made between the viruses
and the diseases they cause.

Acute, persistent, and latent infections of the CNS, which produce acute or chronic (static or
progressive) disease, are differentiated from those infections defined initially by Sigurdsson as "slow
infections" . Simply stated slow infections are characterized by:

1. a long incubation period between exposure to the infectious agents and development of clinical
disease (months-years),

2. a protracted ingravescent clinical course resulting usually in death (weeks-months),

3. a localization of pathology usually to one organ system. Slow infections are caused by both
conventional viruses and unconventional agents.

The clinical and pathological changes in affected animals are directly related to the organ concentration
of virus and infectious agent. The prolonged incubation period is probably related to the gradual
accumulation of a critical number of virus-affected cells . Conventional viruses such as paramyxoviruses
(measles), papovaviruses (IC), and retroviruses (visna) may cause slow encephalitic and demyelinating
diseases. Unconventional agents associated with scrapie, transmissible mink encephalopathy, kuru, and
Creutzfeldt-Jakob disease cause slowly progressive noninflammatory spongiform encephalopathies in
animals and man . However, a conventional virus (murine neurotropic retrovirus) has been recently
shown to cause a similar encephalomyelopathy in mice . How slow infections result in disease provides
fascinating insight to biological interactions.

Slow Viruses and Prions

Slow infectious diseases are a large group of related neurodegenerative conditions, which affect both
humans and animals. The diseases are caused by a heterogeneous group of agents consisting of
conventional viruses and the unconven-tional agents that are called prions.The term “slow” refers to the
disease process and not to the replication of the viruses that cause the slow disease. Replication rate of
virus is similar to that of most other viruses.

A list of slow infectious diseases caused by prions and conventional viruses is presented

Two main groups of slow virus disease. The groups are:

1. Animal Infection 2. Human Infection.
Slow Virus Disease: Group # 1. Animal Infection:
a. Visna:
It is caused by viruses which are classified under the family lendviridae (See AIDS) as retro viruses and
also cause a demyelinating disease in sheep with incubadon period of 2 years. Pathological changes are
observed in brain, lungs, and reticulo-endothelial system.The disease has an insidious onset with
paresis, total paralysis and death. The virus can be isolated from CSF, saliva or blood of infected sheep
and by tissue culture of choroid plexus. CNS manifestation appears to be an antigen-antibody reaction
on the surface of infected glial cells.

b. Maedi:

Maedi virus is closely related to visna and belongs to subfamily lendviridae. Incubation period is about 2-
3 years. Maedi is a slowly progressive haemorrhagic pneumonia of sheep with fatal termination.

c. Scrapie:
It is a slow virus encephalopathy of sheep. Different breeds of animals are susceptible to scrapie.
Incubation period is 2 years. The infection remain confined to nervous system and exhibits reactive
astrocytosis. The animal becomes irritable and later dies of paralysis. The virus has been maintained in
brain tissue explant cultures by serial passages.

d. Mink:
Mink encephalopathy is similar to scrapie in all aspects except that it occurs in minks. The causative
agent may be a strain of scrapie virus.

Slow Virus Disease: Group # 2. Human Infection:

a. Kuru:
It is a unique disease affecting only the members of cannibalistic fore tribe of Eastern highlands of New
Guinea. It is a slow viral infection with an incubation period of 5-10 years and is transmitted by the tribal
practice of eating infected brains of relatives after a “non- sterilising” ritual cooking.
Grey matter of CNS is degenerated, most marked in cerebellum. This degeneration causes progressive
ataxia and tremors. The disease ends fatally in 3-6 months.

b. Creutzfeldt-Jacob Disease (CJD):

It is a sub-acute encephalopathy which develops gradually and is characterised by progressive dementia,
epilepsy, myoclonus and extrapyramidal motor neuron signs. It may be accidently transmitted to man
from corneal transplant from infected inadequately sterilised neurological instruments and implanted
ECG electrodes.

c. Sub-Acute Sclerosing Pan-Encephalitis (SSPE):

 It is a rare disease of children and young adults and develops as a very late complication of measles
many years after the initial infection. The disease is characterised by slowly progressive demyelination in
the CNS with gradual loss of mental and motor function and as a result there is death in 1-3 years.

Electron microscopy and serological test of brain cells of SSPE patients show measles virus infection. A
defective virus closely resembling measles virus has been isolated from lymph node and brain material
by co-cultivation with He La cells.Long after administration of live measles virus vaccine, SSPE may also
develop. Similar illness may rarely occur in parents with congenital rubella. SSPE may represent a
tolerant infection of latent measles virus due to defective CMI.

d. Progressive Multi-Focal Leuco-Encephalopathy (PML):

In old patients whose immune system is impaired as a result of malignancy (chronic leukaemia,
Hodgkin’s disease lymphoma) or immunosuppression, PML is a progressive demyelinating disease
(multifocal encephalopathy) resulting from infection of oligodendrocytes by papova virus.PML is a rare
complication of CNS and is characterised by progressive loss of motor function, speech and vision —
death occurs in 3-4 months.

Transmission

The transmission of slow virus infections can occur through a variety of routes, depending on the
specific virus. Here are some of the most common modes of transmission:

 Direct contact: This can involve contact with infected bodily fluids, such as blood, saliva, or cerebrospinal
fluid. For example, HIV can be transmitted through sexual contact, sharing needles, or from mother to
child during pregnancy, childbirth, or breastfeeding.
 Indirect contact: This can occur through contact with contaminated objects, such as needles or surgical
instruments. For example, hepatitis B can be transmitted through sharing razors or toothbrushes.
 Aerosols: Some slow viruses can be transmitted through the air in tiny droplets, such as coughs or
sneezes. For example, measles can be transmitted in this way.
 Vectors: Some slow viruses are transmitted by insects or other animals. For example, West Nile virus is
transmitted by mosquitoes.

Symptoms:

 Fatigue and general malaise: Persistent tiredness that isn't relieved by rest and worsens over time.
 Headaches: Frequent or severe headaches that become more pronounced and don't respond well to
typical painkillers.
 Muscle weakness or stiffness: Gradual weakening of muscles, difficulty performing daily activities, and
muscle stiffness that's not related to injury or exercise.
 Cognitive changes: Problems with memory, concentration, learning, or decision-making that worsen
over time.
 Sensory changes: Blurred vision, double vision, hearing loss, or changes in taste or smell.
 Sleep disturbances: Difficulty falling asleep, staying asleep, or experiencing nightmares.
 Mood changes: Depression, anxiety, irritability, or personality changes.
 Unexplained weight loss or gain: Losing or gaining weight without any significant changes in diet or
exercise.

Symptoms specific to certain organs or systems:

 Neurological: Tremors, seizures, difficulty speaking or swallowing, balance problems, or gait

disturbances.
 Respiratory: Persistent cough, shortness of breath, or chest pain.
 Digestive: Chronic diarrhea, nausea, vomiting, or abdominal pain.
 Skin: Rashes, bumps, or other skin changes that persist or worsen.

Pathogenesis
The pathogenesis of these infections is complex and not fully understood, but it is believed to involve
the following key steps:

1. Entry and transmission: Slow viruses can be transmitted through various routes, including:
o Direct contact: Exposure to infected tissues or fluids, such as through blood, saliva, or cerebrospinal
fluid.
o Iatrogenic transmission: Accidental transmission through medical procedures like corneal transplants or
contaminated surgical instruments.
o Genetic inheritance: In some cases, mutations in specific genes can predispose individuals to developing
slow virus infections.

2. Propagation: Once inside the host, the virus replicates slowly and spreads throughout the nervous
system. Unlike typical viruses, slow viruses do not produce new viral particles but instead convert
normal cellular proteins into infectious prions. Prions are misfolded protein molecules that can induce
the misfolding of other normal proteins, leading to cellular damage and dysfunction.
3. Incubation period: The incubation period for slow virus infections can range from months to decades,
depending on the specific virus and host factors. During this time, the virus gradually spreads and
accumulates in the nervous system, but there may be no noticeable symptoms.

4. Neurodegeneration: As the infection progresses, the accumulation of misfolded prions leads to

neuronal damage and cell death. This results in the progressive decline of cognitive function, movement,
and other neurological functions.

Treatment

1. Antiviral medications:In some cases, antiviral medications may be able to help control the replication
of the virus and slow down the progression of the disease. However, this is not always effective, as some
slow viruses are resistant to antiviral drugs.

2. Immune system support:Because slow viruses often exploit weaknesses in the immune
system, treatments that boost the immune system may be helpful. This may include medications such as
interferon or interleukin-2, as well as lifestyle changes such as getting enough sleep, eating a healthy
diet, and exercising regularly.

3. Supportive care:As there is no cure for most slow virus infections, the focus of treatment is often on
managing symptoms and providing supportive care. This may include pain medication, physical
therapy, and occupational therapy.

4. Experimental therapies:A number of experimental therapies are being investigated for the treatment
of slow virus infections. These include gene therapy, stem cell therapy, and anti-prion drugs.

Prevention
Preventing slow virus infections, also known as prion diseases, is challenging due to their complex
nature and long incubation periods. However, several strategies can help reduce the risk:

General preventative measures:

 Avoid contact with infected tissues and fluids: This includes avoiding contact with the brain, spinal
cord, and other neurological tissues of infected individuals or animals.
 Practice good hygiene: Wash your hands thoroughly and regularly with soap and water, especially after
handling potentially contaminated materials.
 Use appropriate personal protective equipment (PPE): Wear gloves, masks, and gowns when handling
potentially infected materials or performing medical procedures.
 Sterilize medical instruments properly: Thoroughly clean and sterilize medical instruments used on
infected individuals.
 Be cautious about medical procedures: Consider avoiding some medical procedures, such as corneal
transplants, that carry a small risk of transmitting prions.
 Educate yourself and others: Sharing information about the risks and prevention of prion diseases can
help raise awareness and protect communities.