(Prepared by: Priya Prakash, 20220901007)
Sunday, April 2, 2023
EARLY VIRUSES
(Prepared by: Noopur, 20220901022)
SMALL POX
What is smallpox?
Smallpox is an acute contagious disease caused by the variola virus, a member of the DNA virus of orthopoxviral family.
It may include the word small but it is one of the most dangers diseases involved from virus. It was one of the most devastating diseases known to humanity and caused millions of deaths before it was eradication.
Should we still worry about smallpox?
It is believed to have existed for at least 3000 years. The World Health Organization declared that smallpox had been eradicated. Currently, there is no evidence of naturally occurring smallpox transmission anywhere in the world. No cases were reported from 1977 to 1980. Through vaccination, the disease was eradicated in 1980.
From where it has come? How it is spread?
There are no natural animal carriers nor natural propagation of variola outside the human body. It is transmitted from person to person, and natural infection occurs by inhalation of respiratory droplets or contact with infected material on mucous membranes.
What are the signs of smallpox?
People who had smallpox had a fever and a distinctive, progressive skin rash. Acute infectious disease that begins with a high fever, headache, and back pain and then proceeds to an eruption on the skin that leaves the face and limbs covered with cratered pockmarks, or pox.
How is smallpox treated?
The vaccine prompts the body's immune system to make the tools, called antibodies, it needs to protect against the variola virus and help prevent smallpox disease.
MEASLES
What is measles?
Measles is a highly contagious, serious disease caused by a virus. Measles is caused by a virus in the paramyxovirus family. It is an enveloped, non-segmented, single-stranded, negative-sense RNA virus, and its genome encodes at least six structural proteins.
How is this caused?
Measles is caused by a virus found in the nose and throat of an infected child or adult. When someone with measles coughs, sneezes or talks, infectious droplets spray into the air, where other people can breathe them in. The infectious droplets can hang in the air for about an hour.
What are the signs of measles?
The first sign of measles is usually a high fever, a runny nose, a cough, red and watery eyes, and small white spots inside the cheeks. The most serious complications include blindness, encephalitis (an infection that causes brain swelling), severe diarrhoea and related dehydration, ear infections, or severe respiratory infections such as pneumonia.
How is measles treated?
Measles can be prevented with MMR vaccine. The vaccine protects against three diseases: measles, mumps, and rubella. The MMR vaccine is very safe and effective.[1], [2]
Source: https://link.springer.com/chapter/10.1007/978-3-030-71165-8_23
References
[1] K. Alibek, “Smallpox: A disease and a weapon,” in International Journal of Infectious Diseases, 2004, vol. 8, no. SUPPL. 2, p. 3. doi: 10.1016/j.ijid.2004.09.004.
[2] A. Misin et al., “Measles: An overview of a re-emerging disease in children and immunocompromised patients,” Microorganisms, vol. 8, no. 2. MDPI AG, Feb. 01, 2020. doi: 10.3390/microorganisms8020276.
BACTERIOPHAGES
(Prepared by: Priya Prakash- 20220901007)
Bacteriophages or phages are viruses that infect bacteria. They are also known as 'Bacteria eater'. They are the most abundant organisms in the biosphere and are a ubiquitous feature of prokaryotic existence. Also they have been beneficial to scientists as tools to understand fundamental molecular biology, vectors of horizontal gene transfer and drivers of bacterial evolution, sources of diagnostic and genetic tools and novel therapeutic agents.
This article describes the roles of phages in different host systems and how modeling, microscopy, isolation, genomic and metagenomic based approaches have combined to provide unparalleled insights into these small but vital constituents of the microbial world.
HISTORY OF BACTERIOPHAGES [1]
1915 – Bacteriophages were discovered by William
Twort.
1917 – Felix d’Herelle discovered that bacteriophages
has the ability to kill bacteria. He observed that filtrates from feces culture
from dysentery patients induced transmissible lysis (disintegration of a cell. He
continued research in two directions: (1) determining the biological nature of
bacteriophages and (2) exploring the use of bacteriophages as a therapy to
treat bacterial infections in a pre-antibiotic era.
1940 – Felix
d’Herelle’s bacteriophage theory become universally accepted.
MORPHOLOGY OF PHAGES
Hexagonal head containing nucleic acid covered by protein coat or capsid. Its 28-100nm in size.
Cylindrical tail which is hollow inside and covered by contractile sheath and terminal hexagonal baseplate. It also contains tail fibers projecting outwards from the baseplate and Tail pins.
How does a Bacteriophage infects Bacteria?
Is it that Easy?
The illustration above depicts how a bacteriophage injects the nucleic acid into the cytoplasm of bacteria.
As the illustration above shows, bacteriophage hijacks the host cell's cellular machinery for their own replication. Now if the environmental conditions are unfavourable, they enter a lytic or virulent cycle, if not then they enter lysogenic or temperate cycle.
In lytic cycle, inside the infected cell, the phage genome replicates producing progeny bacteriophages. These rupture the bacterial cell wall and progenies are released to the adjacent cells and the lytic cycle is repeated.
In lysogenic cycle is a way of viral reproduction that involves integrating viral DNA into host DNA. Once the bacterial cell is infected, the viral DNA inserts itself, or incorporates itself into the host DNA, rather than staying separate.
One of the main difference between the lytic stage and lysogenic cycle is that lytic cycle results in the immediate formation of multiple copies of the virus. But in the lysogenic cycle, the viral DNA replicates only when the host cell does. It spreads from the host to the daughter cells. This is a slower process but benefit is that the viral DNA is safer and it can avoid detection for longer periods of time than it can in the lytic phase.
The evolution of several toxigenic pathogens depended extensively on bacteriophage infections and exchanges of DNA. Examples include C. diphtheriae (causes diphtheria), S. pyogenes (causes strep throat and scarlet fever), and C. botulinum (causes food poisoning or botulism)[2].
So are there any Importance of these in our Life? Fortunately Yes.
- Extensively used in genetic engineering as cloning vectors.
- Used for natural removal of bacteria from water
bodies.
- Used to combat infections caused by antibiotic-resistant
bacteria.
- Used to eliminate superbugs that form biofilms present on implanted medical devices.
- Used to treat ready-to-eat meats, fish, poultry, and soft cheeses with bacteriophages in order to eliminate foodborne pathogens.
Any future prospects?
Research
on bacteriophages is reviving, with an emphasis on the phages themselves rather
than their molecular processes. Some of the practical issues such as how to use
phages to treat human diseases, how to get rid of phage pests in the food
business, and what part they play in the development of human diseases, are
being addressed. Phages are also being employed to investigate fundamental
biophysical and molecular issues [3].
References
RETROVIRUSES
(Prepared by: Srushti Bhoite - 20220901003)
WHAT IS A RETROVIRUS?
A retrovirus is a virus that uses RNA as its genetic material. Upon infection with retrovirus a cell converts RNA into DNA which is inserted into host cell. The cell then produces more retroviruses which infect other cells.
Source: https://1.bp.blogspot.com/-
HISTORY AND IMPORTANCE
Fifteen years ago retroviruses were studied to use animal models for studying human cancer. The historical importance of retroviruses in discovery of cancer genes is widely appreciated. The central goals of retrovirology are treatment and prevention of AIDS and use of retroviruses as gene delivery devices.
REPLICATION PROCESS
Let’s consider example of HIV to understand replication of retroviruses:
1] Attachment- virus binds to receptor on the host cell surface. In HIV this receptor is found on surface of immune cells called CD4 T cells.
2] Entry - envelope surrounding HIV fuses with membrane of host cell which allows the virus to enter host cell.
3] Reverse transcription – It uses reverse transcriptase enzyme to convert RNA genetic material into DNA.
4] Genome integration - the viral DNA travels through nucleus, the viral enzyme integrase is used to insert viral DNA into host cell’s DNA.
5] Replication - once DNA is inserted into host cell’s genome it uses host cell’s machinery to produce new viral components like viral RNA and proteins.
6] Assembly - the viral components combine close to cell surface and begin to form new HIV particles.
7] Release – new HIV particles push out from host cell surface and forms another mature HIV particle with the help of viral enzyme protease. Once outside the cell these particles can infect other CD4 T cells. [1]
Source:https://www.genome.gov/sites/default/files/media/images/tg/retrovirus.jpg
References
[1] G. Rozera et al., “Analysis of HIV quasispecies and virological outcome of an HIV D+/R+ kidney–liver transplantation,” Virol J, vol. 19, no. 1, Dec. 2022, doi: 10.1186/s12985-021-01730-w.
EMERGING VIRUSES
(Prepared by: Isha Gaikwad, 20220901015)
Newly emerging viruses such as the Ebola virus, severe acute respiratory syndrome (SARS)-, Middle East respiratory syndrome (MERS)-coronavirus, and the avian influenza virus are serious threats to public health. The swine flu pandemic in 2009 reminded us of the Spanish flu that killed over 40 million people. Newly emerging viruses could be either a novel previously undescribed virus or a variant of a previously known virus. Variants of previously described viruses are also called "remerging viruses" and can cause new epidemics with considerable virulence. The influenza virus that caused the 2009 pandemic was a variant of an existing virus.
Public health authorities are increasingly relying on quarantine at airports and seaports to monitor the emergence of new viruses and their transmission due to the expansion of international trade and travel.
EBOLA VIRUS
Ebola outbreaks have been documented since the first one in 1976. Ebola fever has a fatality rate that is around 90%. Ebola outbreaks have mostly only occurred in Africa. Due to the high case fatality rate and quick patient death, there is little chance that Ebola will spread and cause a broad epidemic.
WEST NILE VIRUS
An effective illustration of the spread of a zoonotic virus spread by mosquitoes as a result of climate change is the WNV5 pandemic in North America. WNV is a flaviviridae family member that is spread through mosquitoes. It also goes by the name arbovirus. It was first discovered in the East African country of Uganda's West Nile subregion in 1937.
SIN NOMBRE VIRUS
In 1993, the "Four Corners" region of the western United States received its first reports of a mysterious respiratory ailment that was killing young Navajo. Investigators began searching for the culprit in rodents when they saw a clinical resemblance to the hantavirus infection that occurred during the Korean conflict (1950–1953). Up to that point, no known hantavirus infections had ever been documented in the US.
Source: https://www.utmb.edu/virusimages/VI/sin-nombre-virus-%28hantavirus%29
NIPAH VIRUS
As it caused an outbreak of neurological and respiratory diseases on a pig farm in peninsular Malaysia in April 1999, the Nipah virus was first discovered there. 1 million pigs were killed, and there were 257 human cases and 105 fatalities as a result of the pandemic. The majority of the human and pig respiratory and encephalitic signs of infection from the Malaysian outbreak.
SARS-CORONAVIRUS (SARS)
The SARS-CoV is the virus that causes ARS, a respiratory virus with zoonotic origins. A SARS outbreak in southern China between November 2002 and July 2003 resulted in 8273 cases and 775 fatalities across several nations. According to the WHO, Hong Kong had the most cases (9.6% death rate).
Source: https://www.news-medical.net/health/The-Naming-System-Behind-SARS-CoV-2.aspx
Why Do New Viruses Emerge?
Why do fresh human pathogenic viruses keep appearing? Most often, outbreaks have been observed to take place in tropical areas devoid of any habitation. The fundamental reason for the creation of novel viruses is thought to be an increase in human contact with wild animals as a result of the extension of the human habitat. Wild animal contact with humans has increased as a result of environmental changes like rainforest development. As a result, viruses that were previously exclusive to rainforests can now infect a new human host.
References
10.1016/B978-0-12-800838-6.00021-7
https://doi.org/10.1142/8268
Saturday, April 1, 2023
SELECTION
(Prepared by: Isha Gaikwaid, 20220901015)
Viruses undergo evolution and natural selection, just like cell-based life, and most of them evolve rapidly. When two viruses infect a cell at the same time, they may swap genetic material to make new, "mixed" viruses with unique properties. For example, flu strains can arise this way. RNA viruses have high mutation rates that allow especially fast evolution. An example is the evolution of drug resistance in HIV.
Have you ever wondered why a different strain of flu virus comes around every year? Or how HIV, the virus that causes AIDS, can become drug-resistant?
The short answer to these questions is that viruses evolve. That is, the "gene pool" of a virus population can change over time. In some cases, the viruses in a population—such as all the flu viruses in a geographical region, or all the different HIV particles in a patient's body—may evolve by natural selection. Heritable traits that help a virus reproduce (such as high infectivity for influenza, or drug resistance for HIV) will tend to get more and more common in the virus population over time.
Let's see what are types of selection seen in evolution of viruses.
1) HOST IMMUNE SYSTEM: The immune system of the host is constantly trying to eliminate viruses. Therefore, viruses that can evade the host's immune system are more likely to survive and reproduce. Over time, this can lead to the evolution of viruses that are better adapted to their host's immune system.
2) DRUG SELECTION: When viruses are exposed to drugs, those that are resistant to the drug are more likely to survive and reproduce. This can lead to the evolution of drug-resistant viruses.
3) TRANSMISSION SELECTION: Viruses that can spread more easily from host to host are more likely to survive and reproduce. This can lead to the evolution of viruses that are better adapted to transmission between hosts.
Source:https: https://www.sciencedirect.com/science/article/pii/S0195670115003679
4) REPLICATION SELECTION: Viruses that can replicate more quickly are more likely to survive and reproduce. This can lead to the evolution of viruses that are better adapted to replicating quickly within a host.
NATURAL SELECTION AND MOLECULAR EVOLUTION IN FUSARIUM GRAMINEARUM
VIRUS 1
We aimed to investigate the evolution and adaptation of Fusarium graminearum virus 1 (FgV1), a positive-sense ssRNA virus that induces hypovirulence in its fungal host. As FgV1 lacks an extracellular life cycle and is transmitted through sporulation or hyphal anastomosis, we conducted mutation accumulation (MA) experiments by serially passaging FgV1 alone or with FgV2, 3, or 4 in F. graminearum to understand its evolutionary dynamics. We hypothesized that the effects of positive selection on the virus would be constrained due to repeated bottleneck events.
Determine whether selection on FgV1 was positive, negative, or neutral, we evaluated both the host fungus's phenotypic traits and the RNA sequences of FgV1. Our results indicated that positive selection acted on beneficial mutations in FgV1, as evidenced by the dN/dS ratio, pNR/pNC ratio, and changes in predicted protein structures. Specifically, we observed evidence of positive selection only in the open reading frame 4 (ORF4) protein of DK21/FgV1 (MA line 1), where mutations at amino acids 163A and 289H affected the entire structure of the protein predicted to be under positive selection.
Source: https://www.frontiersin.org/articles/10.3389/fmicb.2021.622261/full
However, our findings also revealed that deleterious mutations played a significant role in FgV1's evolution during serial passages. The relationship between changes in viral fitness and the number of mutations in each MA line showed that some deleterious mutations led to a decline in fitness. Additionally, we observed that some mutations in MA line 1 were unique and not shared with any of the other four MA lines (PH-1/FgV1, PH-1/FgV1 + 2, PH-1/FgV1 + 3, and PH-1/FgV1 + 4), indicating that evolutionary pathways of the virus might differ with respect to hosts and co-infecting viruses. We suggested that mutational robustness and other unidentified factors could also contribute to the observed differences among MA lines. Thus, further research is needed to clarify the effects of virus co-infection on the adaptation or evolution of FgV1 in its environments.
References
https://doi.org/10.3389/fmicb.2020.600775
Wednesday, March 29, 2023
POPULATION SIZE
(Prepared by: Noopur, 20220901022)
How does population size affect viruses?
The spread of deadly virus can be enhanced with the increasing
number of human beings.
Population genetic diversity plays a prominent role in viral
evolution. This diversity is subsequently modulated by natural selection and
random genetics drift, whose action in turn depends on population size.
What happens if virus mutation take place due to
population size?
Virus mutations create genetic
diversity, which is subject to the opposing actions of selection and random
genetic drift, and this is affected by the size of the virus population. The genetic diversity can lead to
negative or positive virus-virus interaction. Size of viral population
determines the genetic drift, which in turn depends on spatial structure,
population size bottlenecks during host-to-host transmission. Therefore,
selection and drift are conditioned by population size.
The high mutation rate of viruses,
coupled with short generation times and large population sizes, allow viruses
to rapidly adapt to the host environment.
What is population size
bottlenecks?
Population bottlenecks leading to a
drastic reduction of the population size, which are common in the evolutionary
dynamics of natural populations; there occurrence is known to have implication
for virus evolution. It occurs when a population size is reduced for at least
one generation.
Source:https://www.google.com/url?
What if population size is large?
Or small?
When the population size is large, selection becomes predominant
and random genetic drift become less common. When the population size is small,
random effects may obscure the effects of selection. The population sizes of
RNA viruses are often very large, factors such as variation in replication
potential among variants, differences in generation time among infected cells
and population bottlenecks, might lead to an effective population size.
Despite virus enormous population sizes, viruses experience
significant genetic drift. This is because the strength of drift depends on the
effective population size, not on the census size.
Viral population genetic diversity plays a major role in ability
of viruses to cause disease. In general pathogens evolve faster than their
hosts owing to their shorter generation times and higher population size
One unique characteristic of viruses is their MOI, which is the
ratio between the number of viruses and the infecting cells. MOI can be subject
to the constantly changing size of the virus population.
The viral evolution creates huge population size within the
infected host. However, this huge population size is punctuated by frequent
bottlenecks.
References
[1] [1] A. Stern and R. Andino, “Viral Evolution: It is All About Mutations,” in Viral Pathogenesis: From Basics to Systems Biology: Third Edition, Elsevier Inc., 2016, pp. 233–240. doi: 10.1016/B978-0-12-800964-2.00017-3.
[2] [2] A. Moya, E. C. Holmes, and F. González-Candelas, “The
population genetics and evolutionary epidemiology of RNA viruses,” Nature
Reviews Microbiology, vol. 2, no. 4. pp. 279–288, Apr. 2004. doi:
10.1038/nrmicro863.
MULTIPLICITY OF INFECTION
(Prepared by: Srushti Bhoite, 20220901003)
It is defined as the ratio of
infectious virions to cells in a culture. When the MOI is high the cell is
infected with multiple viruses but when MOI is low the cell is infected with
only one virus. In
recombining viruses if MOI is higher it would lead to higher recombination and
eventually it will lead to more efficient selection, removal of deleterious
alleles and emergence of strains with more virulent phenotype.
It may have contrary effects
like inferior genotypes are rescued and maintained in population.
Complementation at high MOI leads to multiplication of defective particles.
High MOI also leads to multiple genomic copies of same gene in one infected
cell. In phage if copy number is one it will be lytic and kill the host cell
and if it exceeds one it becomes lysogenic and host cell remains alive.
The number of phage infecting
each bacterium could be calculated from Poisson equation: P(n)
= (m*n × e-m)/n! where P(n) is the probability
that the cell will be infected with exactly “n” phage and “m” is the average
number of phage per cell (that is MOI).
High MOI leads to complex
effects on genome selection Distribution of viral particles at different sites
of an infection are unknown and will affect MOI and efficiency of selection. The
population with highest fitness in the original host does not adapt well in new
hosts whereas low frequency genotypes from original host may adapt well in new host.
Different types of viruses will be affected differently by MOI.
Source: https://kb.10xgenomics.com/hc/article_attachments/360043450932/MOI.png
References
[1] [1] P. Shabram and E. Aguilar-Cordova,
“Multiplicity of infection/multiplicity of confusion,” Molecular Therapy,
vol. 2, no. 5. pp. 420–421, 2000. doi: 10.1006/mthe.2000.0212.
[2] A. Stern and R. Andino, “Viral Evolution: It is All About Mutations,” in Viral Pathogenesis: From Basics to Systems Biology: Third Edition, Elsevier Inc., 2016, pp. 233–240. doi:10.1016/B978-0-12-800964-2.00017-3.
[2] A. Stern and R. Andino, “Viral Evolution: It is All About Mutations,” in Viral Pathogenesis: From Basics to Systems Biology: Third Edition, Elsevier Inc., 2016, pp. 233–240. doi:10.1016/B978-0-12-800964-2.00017-3.
Sunday, March 26, 2023
ROLE OF MUTATION IN EVOLUTION
(Prepared by:Priya Prakash, 20220901007)
Viral evolution is driven by the accumulation of genetic changes, which can lead to the emergence of new strains or subtypes of the virus. Mutations play a significant role in viral evolution. Mutations can affect various aspects of viral biology, such as virulence, transmission, and host range, and can also lead to drug-resistant strains. Understanding their impact is essential for developing effective strategies to control viral infections.
But what’s Mutations in Viruses?
Mutations are the basis for evolution and natural selection. An alteration in the genetic material (the genome) of a cell of a living organism or of a virus that is more or less permanent and that can be transmitted to the cell’s or the virus’s descendants is known as Mutation. Viruses have high mutation when compared to any life form. This helps it to rapidly evolve and adapt quickly to the host system.
Are Mutations Good For Viruses?
Mutations in viruses, when they make copies of themselves can be both beneficial and harmful. Some such changes can lead to efficient reproduction or lead to dead ends or harmful outcomes which limit an organism’s ability to survive. We all know that there was once confusion on whether viruses should be considered as living or non-living organisms. But their mutation ability was considered as the most compelling arguments for viruses to be classified as living organisms.
But Why Mutations?
Mutations help viruses to be more effective than the previous generation in moving from host to host, speed up reproduction and thereby extend its life. It also helps them to be more effective in adhering to host surfaces. The example for this is quite well known, the spike protein of COVID-19. Mutations also have the ability to increase the probability of viruses evading the immune responses and vaccines.
The illustration below depicts how mutation happens in a virus.
Let’s discuss about variations in genes due to mutations.
Genetic variety is produced by viral mutations but comes under the pressure of selection and random genetic drift which is directly influenced by the number of virus populations. Large populations will exhibit selection more frequently and less frequently than small populations. Thus, harmful alleles will be successfully eliminated from the population while adaptive alleles will have a chance to rule the community. Random effects, however, could mask the effects of selection in small populations. The population's frequency of mildly harmful alleles may unexpectedly increase under these circumstances, while adaptive alleles could accidentally disappear.
The abundance of mutants, which is also referred to as a "quasispecies," has the capacity to encode viruses with increased treatment resistance or the capacity to elude neutralising antibodies produced by the host. This challenges efforts to develop efficient vaccinations since evolution has the potential to significantly expand the number of virus serotypes that are present in human populations. In addition, viruses' special capacity for change enables them to pass over barriers separating species, leading to zoonotic diseases [1].
The mutation together with selection will determine which mutations will survive in the viral population.
Have you heard about Lethal Mutagenesis?
Lethal mutagenesis is a phenomenon in which an increase in the mutation rate of a virus or other pathogen leads to its extinction. It has been proposed as a potential therapeutic approach for treating viral infections, including those caused by HIV, influenza, and hepatitis C. However, there are many challenges associated with implementing this approach, such as balancing selective pressure on the virus with the potential for it to evolve resistance, and concerns about the safety and efficacy of the mutagenic agents themselves [2].
References
[1] R. Sanjuán and P. Domingo-Calap, “Mechanisms of viral mutation,” Cellular and Molecular Life Sciences, vol. 73, Mar. 2016, doi: 10.1007/s00018-016-2299-6.
[2] A. Stern and R. Andino, “Chapter 17 - Viral Evolution: It Is All About Mutations,” in Viral Pathogenesis (Third Edition), Third Edition., M. G. Katze, M. J. Korth, G. L. Law, and N. Nathanson, Eds. Boston: Academic Press, 2016, pp. 233–240. doi: https://doi.org/10.1016/B978-0-12-800964-2.00017-3.
[2] A. Stern and R. Andino, “Chapter 17 - Viral Evolution: It Is All About Mutations,” in Viral Pathogenesis (Third Edition), Third Edition., M. G. Katze, M. J. Korth, G. L. Law, and N. Nathanson, Eds. Boston: Academic Press, 2016, pp. 233–240. doi: https://doi.org/10.1016/B978-0-12-800964-2.00017-3.
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