The Biology of Viruses
• 程洪强,博士,副教授,浙江大学医学院病理与病理生理学系• 研究兴趣:心血管生物学与心血管病分子病理• 电话:13735827063 电邮:[email protected]• 主页:http://mypage.zju.edu.cn/hqcheng• 地址:医学院科研楼A324
A lethal RNA virus9 infected and 3 dead
Hanta Viruse
汉坦病毒
H7N9
The Origin and Evolution of Viruses (Living or nonliving is a question)
• Viruses have been found that infect every form of life, as well as other viruses.
• Originated from naked bits of cellular nucleic acids (?)
• DNA sequencing and bioinformatics analysis (most human RNA viruses emerged less than 1,000 years ago)
Concepts• General information
• Classification
• Structure
• Amplification/reproduction
• Viral disease and anti-virus therapy
• Impact on biological research
The Definition of Viruses (病毒)
• A virus is little more than DNA (or sometimes RNA)
enclosed by a protective coat, which is often
simply protein. To produce more viruses, a virus
must infect a cell and take over the cell’s
metabolic machinery. (A borrowed life) (NOT
Computer Virus)
• A virus is an infectious particle consisting of little
more than genes packaged in a protein coat.
The International Committee on Taxonomy of Viruses has
catalogued a total of 2618 known viruses or viroids that
either affect eukaryotes or prokaryotes in their latest list
(http://talk.ictvonline.org/files/ictv_documents/m/msl/4440.a
spx).
烟草花叶病毒 腺病毒 噬菌体
Electron micrographs of highly purified preparations of some viruses.(a) Adenovirus. (b) Rotavirus. (轮状病毒)(c) Influenza virus (courtesy of George Leser). (d) Vesicular stomatitis virus. (水疱性口腔炎病毒)(e) Tobacco mosaic virus. (f) Alfalfa mosaic virus. (苜蓿花叶病毒)(g) T4 bacteriophage. (h) M13 bacteriophage.
Viruses
Virus is Tiny
Classification
• Host range (host specificity): plant, animal and phage
• They are called either a DNA or RNA virus depending on the type of nucleotide in the make-up.– Double stranded DNA– Single stranded DNA– Double stranded RNA– Single stranded RNA
• They may be linear or circular
• The smallest have only 4 genes and largest have several hundred (giant viruses), even more.
Classification
多瘤病毒
疱疹病毒
痘病毒
细小病毒
呼吸道肠道病毒
小RNA病毒
冠状病毒
黄病毒
外衣病毒
丝状病毒
禽流感病毒
副粘液病毒莎草弹状病毒
反转录病毒
Protein synthesis----capsid
DNA replication----DNA
Amplification
Amplification
Lytic or Lysogenic Cycles
• The Lytic Cycle– Culminates in the
death of the host cell– Virulent viruses
reproduce only by lytic cycle.
– Natural selection favors bacterial mutations with receptor sites that are resistant to a particular phage or that have restriction enzymes to destroy the phages.
• The Lysogenic Cycle
– Replication of the viral genome without destroying the host cell.
– A temperate virus may reproduce by either cycle.
– Lambda virus: resembles T4 but only has a single short tail fiber
• While phages have the potential to wipe out a bacterial colony in just hours, bacteria have defenses against phages.– Natural selection favors bacterial mutants
with receptors sites that are no longer recognized by a particular type of phage.
– Bacteria produce restriction nucleases that recognize and cut up foreign DNA, including certain phage DNA.
• Modifications to the bacteria’s own DNA prevent its destruction by restriction nucleases.
– But, natural selection favors resistant phage mutants
The Interactions Between Viruses and its Hosts: Evolution
The Evolution of Viruses is a Myth
• Plasmids transposons and viruses share an important feature: they are mobile genetic elements.
• Read information from viral genomes
• Mimivirus (400 nm, 1000 genes)
RNA Virus Replication
Viral Persistence(持续性感染)
• Acute viral infection, chronic infection, latent infection
• Ability to hide from host immune systems
• Persistence is a capability acquired and strengthened in the process of evolution of many viruses that is the means of maintenance of species
Viral Persistence1. The virus may disguise itself or mimic properties of the host’s normal
cells.2. The virus may infect a small subset of cells situated in the brain,
reproductive organs, and parts of the eye and joints that are immunologically privileged, that is free from the usual scrutiny of the immune system.
3. The virus may paralyze or destroy certain immune functions directly responsible for its elimination.
4. It may integrate itself into the genetic make-up of the cell, thereby insuring itself subsistence as long as the normal cell is not eliminated.
5. The virus may have genetic controlling elements that regulate and limit its expression.
6. The virus may have an ability to continually change itself on a regular basis such that the immune system is never able to “catch up.”
7. More
Surprisingly, it appears that not just retroviruses but almost all types of viruses can become endogenous
Viroids and prions
Viroid: An infectious particle, similar to but smaller than a virus, that consists solely of a strand of RNA and is capable of causing disease in plants.
Prion: A prion in the Scrapie form (PrPSc) is an infectious agent composed of proteinin a misfolded form.
Emerging Viruses
Poliovirus(脊髓灰质炎病毒)
• ssRNA, serves as mRNA
• Isolated at 1909 and sequenced at 1981
• Poliomyelitis or infantile paralysis
• Poliovirus receptor (CD155), endocytosis
• One long polypeptide for 10 proteins
• Each dying cell can release up to 10,000 polio virions.
Polio Vaccines
• 1948, John Enders and Thomas Weller
(1954 Nobel,病毒学研究)
• 1952, Salk vaccine, inactivated
(沙克疫苗)
• 1950s-60s, Oral vaccine, worldwide
(沙滨疫苗)
Countries
Year-to-date 2012 Year-to-date 2011
Total in2011*
Date of mostrecent caseWPV1 WPV3 W1W
3 Total WPV1 WPV3 W1W3 Total
Nigeria 67 16 83 19 7 26 62 15-Aug-12
Pakistan 26 2 1 29 76 1 77 198 21-Jul-12
Afghanistan 17 17 18 18 80 21-Jul-12
India 1 1 1 13-Jan-11
Chad 5 5 106 3 109 132 14-Jun-12
DR Congo 76 76 93 20-Dec-11
Angola 4 4 5 07-Jul-11
Niger 1 1 2 5 22-Dec-11
CAR 4 08-Dec-11
China 4 4 21 09-Oct-11
Guinea 2 2 3 03-Aug-11
Kenya 1 1 1 30-Jul-11
Côte d'Ivoire 35 35 36 24-Jul-11
Mali 7 7 7 23-Jun-11
Congo 1 1 1 22-Jan-11
Gabon 1 1 1 15-Jan-11
Total 115 18 1 134 308 56 0 364 650Total in endemic countries 110 18 1 129 114 8 0 122 341
Total
Data in WHO as of 06 Sep 2011 for 2011 data and 04 Sep 2012 for 2012 data.
Case breakdown by country
1988, 350000 cases
HIV (human immunodeficiency virus)
• ssRNA, retrovirus, reverse transcriptase
• Discovered at 1980s, AIDS (acquired immunodeficiency syndrome)
• Treatments: vaccines, antiviral drugs (ATZ and cocktails)
• Vaccines are successful in fighting to smallpox virus(天花), hepatitis B, rubella(麻疹), mumps(流行性腮腺炎)……but, not for HIV now.
Life Cycleof HIV
Adapted from WHO
HIV Researches and Medicines
Demberg T, 2012, controlling HIV/AIDS epidemics: Current status and global challenges
Vaccine(疫苗)
• A vaccine is a harmless variant or derivative of a pathogen that stimulates the immune system to mount defenses against the harmful pathogen
SUMMARY AND CONCLUSION
As briefly summarized by this review the substantial progress made in AIDS treatment has stimulated the concept of “treatment as prevention.” Additionally, vaccine development has picked up momentum due to new discoveries and the modest success of the RV144 clinical trial in Thailand. However, to achieve global control of HIV/AIDS infection in the absence of a highly efficacious vaccine or cure, a combination of multiple preventive measures will need to be continuously applied. Further investigation of all elements of the host immune system, both innate and adaptive, as well as development of novel treatment strategies should proceed in order to insure strong control of the AIDS pandemic and eventual eradication of the disease.
Demberg T, 2012, controlling HIV/AIDS epidemics: Current status and global challenges
HIV Researches and Medicines
Viruses as Bioresearch tools
1. Biological researches 2. Powerful toolslViral proteins (retrotranscriptase, RT-PCR and
Cre recombinase, homologous recombination and genetic modification)lDelivery tools: Transfection and overexpression
(viral vectors, adenovirus, lentivirus) and viruses mediated therapy
Example: RetrovirusReverse transcriptionReverse transcriptase
G U A A U C C U CAAAAAAAAAAAAAAAReverse
transcriptase
mRNA
cDNATTTTTTTTTTTTTTT
逆转录polyT引物
Retrotranscription
RTase
RT-PCR
Example: Cre-Loxp and Gene Modification
• Cre recombinase: a DNA recombinase from bacteriophage P1• Loxp site: a 34-bp DNA sequence
5' - ATAACTTCGTATA - ATGTATGC - TATACGAAGTTAT - 3'
3' - TATTGAAGCATAT - TACATACG - ATATGCTTCAATA - 5'• Genetic manipulation
Example:Gene Therapy
There are an estimated 1031 viruses on Earth. That is to say: there
may be a hundred million times more viruses on Earth than there
are stars in the universe. The majority of these viruses infect
microbes, including bacteria, archaea, and microeukaryotes, all of
which are vital players in the global fixation and cycling of key
elements such as carbon, nitrogen, and phosphorus. These two facts
combined—the sheer number of viruses and their intimate
relationship with microbial life—suggest that viruses, too, play a
critical role in the planet’s biosphere.
Key Points
1. Definition (living or nonliving is a question)
2. Structure
3. Amplification/life cycle
4. Illness and treatments, anti-viral drugs and vaccines
5. Contributions to biological research
References:
1. Must read: Campbell Biology: P427-441
2. May read: • Takashi Yamada, Giant viruses in the environment: their origins and
evolution, Curr Opin Virol. 2011 Jul;1(1):58-62.
• Thorsten Demberg and Marjorie Robert-Guroff, Controlling the HIV/AIDSepidemic: current status and global challenges, Front Immunol. 2012;3:250.
• Philippe N, Legendre M, Pandoraviruses: amoeba viruses with genomes up to 2.5 Mb reaching that of parasitic eukaryotes. Science. 2013, 341:281-6.
References:
• How many mammalian viruses? (http://www.the-scientist.com/?articles.view/articleNo/37327/title/How-Many-Mammalian-Viruses-/)
“In my life time, we might be able to find every mammalian virus that might infect us,” said Daszak. “And once you know your enemies, you can start to do something about them.”
• Mark Woolhouse, Fiona Scott, Zoe Hudson, Richard Howeyand Margo Chase-Topping. Human viruses: discovery and emergence. Phil. Trans. R. Soc. B, vol. 367 :2864-2871
(There are 219 virus species that are known to be able to infect humans. )
References:
Going ViralFrom therapeutics to gene transfer, bacteriophages offer a sustainable and powerful method of controlling microbes. (http://www.the-scientist.com/?articles.view/articleNo/37208/title/Going-Viral/)