MICROBIOLOGY 1 (BMY3101)

MY ADOPTED MICROBE

BY : JOSELIA VINCENT

COMMON NAME: Human CMV

MICROBE’S NAME: Human cytomegalovirus (HCMV)

CLASSIFICATION

HCMV belongs to the Herpesvirisidae (Herpesviruses)

Within subfamily of betaherpesvirinae, HCMV also includes the herpes simplex viruses, varicella-zoster virus (cause chickenpox and shingles), Epstein-Barr virus (cause infectious mononucleosis), human herpes virus 6,7 and 8

Two main systems of classification used: International Committee on Taxonomy of Viruses (ICTV) and the Baltimore classification

ICTV Classification categorizes viruses into an order, family, subfamily, genus, and species. The six orders that have been established so far include the Caudovirales, Herpesvirales, Mononegavirales, Nidovirales, Picornavirales, and Tymovirales. HCMV belongs to the Herpesvirales order, which includes other dsDNA (double-stranded DNA) viruses.

The Baltimore classification categorizes viruses according to their nucleic acid type (RNA or DNA), strand, sense (comparable polarity), and method of replication. There are seven group to classified HCMV.

DESCRIPTION

Cytomegalovirus (from the Greek cyto-, "cell", and megalo-, “large") is a viral genus of the viral family known as Herpesviridae or herpesviruses. It is typically abbreviated as CMV.

The species that infects humans is commonly known as Human CMV (HCMV) or Human herpesvirus-5 (HHV-5).

The name cytomegalovirus is derived from the associated enlargement of cells following infection.

Complete CMV particles have a diameter of 120-200 nm. The virus has a double stranded DNA genome that is covered with an iscosahedral shaped protein complex that is known as the capsid, surrounded by phospholipid rich envelope .

• The DNA and the capsid together make up the nucleocapsid which is then coated with a layer of protein known as the tegument. It aid in reproduction and concealment from the

host’s immune system.

• The membranous envelope that surrounds the tegument is made by the Golgi bodies in the host cell. The viral glycoproteins assist in entrance of the virus, development of new viruses, and spreading of the virus from one cell to the next.

• A common virus which infects most people at some time during their lives but rarely causes obvious illness. This is particularly true when infection occurs in childhood.

• Most individuals are infected in the first few years of life and by adulthood 70-90% of people have IgG antibodies.

• However, as is the case with other viruses in the herpes family, when humans are infected it remains dormant in the body for the rest of their life when it is not active.

ECOLOGY (INCLUDING PHATOGENESIS)

• Like all viruses, HCMV cannot grow or reproduce on its own. In order to make new copies of itself it must infect the cells of a living organism. HCMV is found in human.

• Transmission of infection of CMV takes place from one person to another, and it is not related with water, food, or animals. This virus is not high contagious. However, it spread among young children.

• Transmission can occur through direct contact with infectious tissues, secretions or excretions (urine, saliva, breast milk, cervical secretions, semen etc); during blood transfusion; and via organ transplantation.

• Infected mothers can transmit the virus to their fetus in utero (transplacental), to newborns at the time of delivery (intrapartum: by contact with the virus in the birth canal), or to infants through breast.

• Sexual transmission has also been reported to occur.

METABOLISM AND NUTRITION

• Of all herpes viruses, HCMV harbors the most genes dedicated to altering (evading) innate and adaptive immunity in the host and represents a life-long burden of antigenic T cell surveillance and immune disfunction.

• The viral life cycle takes approximately seventy two hours. After the initial fusion of the viral envelope with the plasma membrane of the cell, the encapsidated virus particle is released into the cytoplasm and within minutes, transits to the nucleus.

• Via active transport through the nuclear pore, the capsid gains entry and viral DNA is deposited. Viral gene expression then occurs in a temporally regulated manner, first with expression of the immediate early genes, followed by the early genes, then, after viral replication has commenced, the late genes.

• All of the immediate early proteins have been shown to be transactivators, with IE1-72 and IE2-86 being the most well characterized. The immediate early genes are required for both early and late gene expression. Early genes generally encode for the factors that the virus requires for replication.

REPLICATION AND REPRODUCTION

Virus Life Cycles

• Viral replication is slow and involves the expression of immediate- early, early, and late genes. Replication occurs in the nucleus of the host cell

• Viruses can only reproduce within a host cell. Without the metabolic enzymes and ribosomes in the host cell, a virus is essentially inert. The two cycles of phage reproduction are the lytic and lysogenic cycles.

Lytic Cycle

• Once a virus enters the host cell, it releases its DNA and capsid proteins. Enzymes within the host replicate the viral genome. While this is occurring, other enzymes in the host cell transcribe the viral genome into viral mRNA, which is used to make more capsid proteins.

• After the viral genomes and capsid proteins are produced, they assemble into new virus particles, which leave the cell in the hopes of infecting other host cells. The host cell dies in this process, so viruses must find new host cells to use for reproduction. CMV is a lytic virus and reproduces in this way.

Lysogenic Cycle

• The lysogenic cycle facilitates phage genome replication without killing the host cell in the process. A phage will first

inject its DNA genome into the host cell, which forms into a circle. The phage DNA then integrates into the bacterial host’s chromosome, which is now called a prophage.

• The host reproduces as usual, but it copies the prophage and sends it to daughter cells. The host continues to reproduce with the prophage in its chromosome and transmit the prophage to the cells it produces.

INFECTION

• CMV is contracted through the passage of bodily fluids from an infected human to an uninfected human. Contact can occur from many sources, such as through the placenta (during pregnancy), blood transfusions, breast milk, organ transplantation, saliva, urine, and sexual transmission. It is estimated that about 50-80 percent of the population will have contracted the virus by the age of 40.

The presence of viral inclusion bodies ("owl eyes") can help

diagnose the presence of a virus.

Symptoms

• The distinctive feature of CMV infection is enlargement of the cell and presence of viral inclusion bodies. Viral inclusion bodies are abnormal structures that can appear in the nucleus and/or cytoplasm during virus multiplication and can be important signals for diagnosing a viral infection.

• When a human is first infected, CMV infects the epithelial cells in the salivary glands, which causes continuous infection and further reproduction and transmission of the virus to other cells in the body.

SYMPTOMS

• Common cold and flu, fever, fatigue, sore throat, and swollen glands. Infection of CMV is typically not the first diagnosis. Therefore, many hosts are unaware they have been infected by the virus.

• Healthy children that become infected with HCMV either show no symptoms or very few symptoms.

• HCMV remains dormant throughout

a person’s life and has the possibility of reactivating, even if no symptoms were present during the first infection.

• In individuals with weakened immune systems, the symptoms of HCMV can be more severe. These can include high fever, pneumonia, hepatitis, encephalitis, myelitis, colitis, uveitis, retinitis, and neuropathy.

• HCMV is an extremely common virus around the world, but no severe epidemics have ever been

recorded.

TREATMENT

• Healthy individuals that do not experience symptoms of CMV do not need medical treatment. Those that experience mild symptoms are able to treat the symptoms (sore throat, fever, etc.) individually as other common viral infections are treated.

• At the current time, there is no drug approved to treat HCMV. However, pediatricians asses and treat children born with the infection according to the symptoms they experience. The brain damage, hearing loss, and other severe problems associated with HCMV are irreversible, but the damage can be managed, just like all disabilities.

Here are a few simple steps you can take to avoid exposure to saliva and urine that might contain CMV:

• Wash your hands often with soap and water for 15-20 seconds, especially after

-changing diapers

-feeding a young child

-wiping a young child’s nose or drool

-handling children’s toys

• Do not share food, drinks, or eating utensils used by young children

• Do not put a child’s pacifier in your mouth

• Do not share a toothbrush with a young child

• Avoid contact with saliva when kissing a child

• Clean toys, countertops, and other surfaces that come into contact with children’s urine or saliva

VACCINES

• Current research has produced a few potential, but unapproved, vaccines to prevent CMV, including some that contain live, weakened strains of the virus, and others that just contain small pieces of the virus. Though CMV is common, it has the potential of producing seriously harmful effects on the afflicted individual. Therefore, finding a CMV vaccine has been given very high priority because of the life-saving and disability-reducing possibilities, especially in newborns.

SIGNIFICANTS

• HCMV do not have beneficial significant but as a virus, they can served as a model for understanding DNA replication, RNA synthesis and protein synthesis.

• Study of viruses has contributed significantly to the discipline of molecular biology.

• Genetic engineering based on the use of viruses an viral enzymes can be conduct

• Overall HCMV can lead diseases to human.

RESEARCHS

1970s

• the group of Fred Rapp reported HCMV to transform normal human embryonal cells in vitro. Although the transformed cell lines exhibited enhanced tumorigenicity in nude mice, the expression of HCMV-specific antigens in the transformed and tumor-derived lines decreased with increasing passage.

• In later studies using normal rodent cells, HCMV (infectious virus or virus DNA) was shown to induce mutations in genes that are critical for malignant transformation. However, viral DNA was not detected in most transformants.

1970s :

• However, this scenario is difficult to prove because it supposes that virus nucleic acids are not retained in transformed cells. In fact, up to now, there is no conclusive evidence for the transformation of normal cells after HCMV infection in humans, and the mechanism by which HCMV might contribute to oncogenesis remains obscure. Today, it is generally accepted that infection of normal permissive cells with HCMV does not result in malignant transformation (cells actively expressing virus no longer divide and eventually die), so that the virus is not considered to be oncogenic.

2002

• They proposed the concept of oncomodulation in which HCMV may favor tumor progression without being an oncogenic virus to explain the frequent presence of HCMV in tumor tissues. Oncomodulation means that HCMV may infect tumor cells and modulate their malignant properties, in a fashion not involving direct transformation. We postulated that tumor cells provide a genetic environment, characterized by disturbances in intracellular signaling pathways, transcription factors, and tumor suppressor proteins, that enables HCMV to exert its oncomodulatory potential, although it cannot be manifested in normal cells.

• Robert Pass, M.D., of the University of Alabama at Birmingham School of Medicine and his colleagues have been experimenting with CMV to find a vaccine for the virus. The team developed a vaccine based on only one CMV antigen and an adjuvent (trigger immune responses for greater vaccine delivery).

• The test consisted of 441 women (CMV-negative) between the ages of 14 and 40. Some women were given a placebo, while others received the vaccine. The results showed that 8% of women in the vaccine group contracted CMV but 14% of women contracted CMV in the placebo group. Out of the 81 children born to mothers in the vaccine group, only one was born with CMV (1%), compared to the 3% of CMV-infected children born to mothers in the placebo group.

• The results of the reduction of congenital CMV was too close to call, but the testing has given researchers promising answers to a potential CMV vaccine.

Human Cytomegalovirus and Autoimmune Disease

By Anne Halenius and Hartmut Hengel, Institute of Virology,

University Medical Center, Albert-Ludwigs-University Freiburg, Hermann-Herder-Straße 11, 79104 Freiburg, Germany (2014)

Overview:

Autoimmune disease (AID) is a complex dysregulation of immunity, resulting in loss of self-tolerance and subsequent assault on endogenous tissue or cells. This is an article about if and how infection with Human cytomegalovirus (HCMV), another human herpes virus, could be linked with certain autoimmune diseases and how both conditions could interfere with each other.

More info at: http://www.hindawi.com/journals/bmri/2014/472978/

REFERENCES

• Campbell, Neil A., and Jane B. Reece. "Microbial Models: The

Genetics of Viruses and Bacteria." Biology. Boston, MA: Pearson

Custom/Benjamin Cummings, 2002. 331-334.

• http://cytomegalovirusproject.wikispaces.com/Current+Research

• Prescott, L.M., Harley, L.M. & Klein, D.A. (2007). Microbiology (7th

Edition). New York: McGraw-Hill, Inc.

• http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/cytomegalovirus-

eng.php

• http://www.cdc.gov/cmv/index.html (cytomegalovirus)

MY THOUGHT

I am very thankful to God as this ‘adopt a microbe’ task was finally done. Throughout doing this task, I found it was quite challenging but yet interesting. I had chose a virus, HCMV as my adopted microbe. I chose virus because I always interested to learn more about viruses as it was a unique microorganism. I found it was a little bit hard to find the

suitable information about virus but I’m glad that I have a chance to know and study about this microbe specifically.

I strongly think that this task is a very good process of learning to all of us as a future microbiologist so that we know and recognize a specific microbe to a particular function. Therefore, I am very thankful to Dr. Wan for giving us this opportunity to adopt our interest microbe and explore about it.

Moreover, I was very happy to do this scrapbook. I admit that I just started to do the scrapbook a week before the date of submission. However, I get a positive impact while preparing it because I can enhance my knowledge and used all my free time to find the information about this microbe. Once again thank you very much to Dr. Wan to guide us throughout this whole time and thanks also to all of my classmates that had ever help

me.

MYSELF

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THANK YOU VERY MUCH! f