Virology Exam 2

Common characteristics of viruses

• Viruses are usually small in size. \n • The smallest of viruses are about 20 nm in diameter, although influenza \n viruses, coronaviruses, and the human immunodeficiency virus have a \n more typical size, about 100 nm in diameter. \n • Average human cells are 10 to 30 μm (microns) in diameter, which means \n that they are generally 100 to 1000 times larger than the viruses that are \n infecting them. \n • However, some viruses are larger than 100 nm. Poxviruses, such as the \n variola virus that causes smallpox, can approach 400 nm in length, and \n filoviruses, such as the dangerous Ebola virus and Marburg virus, are only \n 80 nm in diameter but extend into long threads that can reach lengths of \n over 1000 nm.

Viruses are ___________, meaning that they are \n completely dependent upon the internal environment of the cell to \n create new infectious virus particles, or virions.

obligate intracellular parasites

The genetic material of viruses can be composed of _________

DNA or RNA

All living cells, whether human, animal, plant, or bacterial, have \n ___________as their genetic material

double-stranded DNA (dsDNA)

Viruses, on the other hand, have ___________, that \n can be composed of DNA or RNA (but not both).

genomes, or genetic material

• Genomes are not necessarily double-stranded, either; some viruses \n have single-stranded DNA (ssDNA) genomes, and viruses with RNA \n genomes can be single-stranded or double-stranded. However, a \n virus will only have one type of nucleic acid genome.

In addition, viral genomes are susceptible to damage by____________, much in the same way that our DNA is. If the nucleic acid genome of the virus is damaged, then it will be unable to produce progeny virions.

ultraviolet radiation or radioactivity

In order to protect the fragile nucleic acid from this harsh environment, the \n virus surrounds its nucleic acid with a protein shell, called the _______, from \n the Latin capsa, meaning “box.”

capsid

capsid

is composed of one or more proteins that repeat over and over \n again to create the entire capsid, in the same way that many bricks fit \n together to form a wall.

Most viruses also have an _________ surrounding the capsid.

envelope

envelope

* is a lipid membrane derived from one of the cell’s membranes, most often \n the plasma membrane, although the envelope can also come from the cell’s endoplasmic \n reticulum, Golgi complex, or even the nuclear membrane, depending upon the virus.

These viruses often have proteins called __________ that function to connect the envelope to the capsid inside.

matrix proteins

A virus that lacks an envelope is known as a _________ virus, also known as a naked virus.

non-enveloped

Each virus also possesses a ___________ embedded in its outermost layer. The virus attachment protein will be part of the capsid of a non-enveloped virus, while it will be embedded in the envelope of an enveloped virus. The virus attachment protein is the viral protein that facilitates the docking of the virus to the plasma membrane of the host cell, the first step in entering a cell.

virus attachment protein

Helical capsid structure

• Each virus possesses a protein capsid to protect its nucleic acid genome \n from the harsh environment. \n • Virus capsids predominantly come in two shapes: helical and icosahedral. \n • The helix (plural: helices) is a spiral shape that curves cylindrically around \n an axis. It is also a common biological structure: many proteins have \n sections with a helical shape, and DNA is a double helix of nucleotides. In \n the case of a helical virus, the viral nucleic acid coils into a helical shape \n and the capsid proteins wind around the inside or outside of the nucleic \n acid, forming a long tube or rod-like structure. The nucleic acid and capsid \n constitute the nucleocapsid. In fact, the protein that winds around the \n nucleic acid is often called the nucleocapsid protein. Once in the cell, the \n helical nucleocapsid uncoils and the nucleic acid becomes accessible.

Advantage of a helical structure:

• There are several perceived advantages to forming a helical capsid. \n • First, only one type of capsid protein is required. \n • This protein subunit is used over and over again to form the capsid. \n • This structure is simple and requires less free energy to assemble than a \n capsid composed of multiple proteins. \n • In addition, having only one nucleocapsid protein means that only one \n gene is required instead of several, thereby reducing the length of nucleic \n acid required. \n • Because the helical structure can continue indefinitely, there are also no constraints \n on how much nucleic acid can be packaged into the virion: the capsid length will be \n the size of the coiled nucleic acid.

Examples of helical structure

• Helical viruses can be enveloped or non-enveloped. \n • All helical animal viruses are enveloped. \n • Rabies virus, measles virus, and Ebola virus.

Icosahedral capsid structure

• The icosahedron is far more prevalent than helical architecture. \n • In comparison to a helical virus where the capsid proteins wind around the \n nucleic acid, the genomes of icosahedral viruses are packaged completely \n within an icosahedral capsid that acts as a protein shell. \n • May appear spherical but are actually icosahedral in structure. \n • An icosahedron is a geometric shape with 20 sides (or faces), each \n composed of an equilateral triangle. \n • An icosahedron has what is referred to as **2–3–5 symmetry**, which is used \n to describe the possible ways that an icosahedron can rotate around an \n axis.

Icosahedral capsid structure:

The proteins that compose the structural unit may form three- \n dimensional structures known as __________that are visible in an \n electron micrograph.

capsomeres

Examples of Icosahedral capsid structure:

• Many viruses that infect animals are icosahedral, including human \n papillomavirus, rhinovirus, hepatitis B virus, and herpesviruses. \n • Icosahedral viruses can be naked or enveloped as well. \n • The type of viral nucleic acid (dsDNA, ssDNA, dsRNA, or ssRNA) does \n not correlate with the structure of the capsid; icosahedral viral \n capsids can contain any of the nucleic acid types, depending upon the \n virus.

A few viruses, however, have a __________ architecture that does not \n strictly conform to a simple helical or icosahedral shape.

complex

Examples of complex viral structures:

• Poxviruses, including the viruses that cause smallpox or cowpox, are \n large oval or brick-shaped particles 200 to 400 nm long. \n • Inside the complex virion, a dumbbell-shaped core encloses the viral \n DNA and is surrounded by two “lateral bodies,” the function of which \n is currently unknown.

\
• **Bacteriophages**, also known as bacterial viruses, are viruses that \n infect and replicate within bacteria. \n • Many bacteriophages have complex structure, such as bacteriophage \n P2, which has an icosahedral head, containing the nucleic acid, \n attached to a cylindrical tail sheath that facilitates binding of the \n bacteriophage to the bacterial cell.

Baltimore classification system

• class I: dsDNA viruses \n • class II: ssDNA viruses \n • class III: dsRNA viruses \n • class IV: positive-sense ssRNA viruses \n • class V: negative-sense ssRNA viruses \n • class VI: RNA viruses that reverse transcribe \n • class VII: DNA viruses that reverse transcribe

How does the ICTV classify viruses

• Virion properties (size, shape, envelope, capsid) \n • Chemical and Physical properties \n • Molecular weight \n • Nucleotide sequence \n • Number and types of different proteins \n • Type of nucleic acid genome; replication strategy \n • Host range \n • Immune properties

Classifying Viruses

Realm: -viria \n Kingdom: -virae \n Phylum: -viricota \n Class: -viricetes \n Order: -virales \n Family: -viridae \n Genus: -virus \n Species: may include common name

\
Realm: Riboviria \n Kingdom: Orthornavirae \n Phylum: Pisuviricota \n Class: Pisoniviricetes \n Order: Picornavirales \n Family: Picornaviridae \n Genus: Enterovirus \n Species: Enterovirus C \n Serotypes/Subtypes; Strains; Isolates; Variants; Mutants; \n Artificially-created laboratory strains

Realm

-viria

Kingdom

\
\-virae

Phylum

\-viricota

Class

\-viricetes

Order

\-virales

Family

\-viridae

Genus

\-virus

Species

may include common name

The seven stages of virus replication are categorized as follows:

1\. Attachment \n 2. Penetration \n 3. Uncoating \n 4. Replication \n 5. Assembly \n 6. Maturation \n 7. Release

* **All viruses must perform all seven stages in order to create new** \n **virions**

Attachment

* the binding of the virus to the host cell

• Plasma membrane is the first location a virus makes contact with a \n cell.

• A virus first interacts with a cell at the plasma membrane \n • Virus attachment protein attaches to a cell surface receptor \n • Binding involves opposing electrostatic forces \n • Some viruses require co-receptors on the cell surface

The interaction:

• is specific \n • for non-enveloped viruses, can \n occur with protruding virus \n attachment proteins or in \n canyons formed by capsid \n proteins \n • for enveloped viruses, will occur \n with virus attachment proteins \n embedded into the envelope \n • determines the tropism of the \n virus

Poliovirus mice

• Mice are not normally infected with poliovirus \n because they do not have the poliovirus \n receptor \n • Transgenic mice were created that expressed \n the human CD155 protein \n • CD155-transgenic mice were able to become \n infected, and viral replication within the brain \n and spinal cord caused paralysis (as occurs \n with human infection)

Penetration

* the crossing of the plasma membrane by the virus

• Following attachment, successful viruses quickly enter the cell to avoid extracellular stresses that could remove the virion, such as the flow of mucus. \n • Penetration refers to the crossing of the plasma membrane by the virus. \n • In contrast to virus attachment, penetration requires energy, although \n the host cell does the work, not the virus.

Different methods of penetration:

• Different viruses take advantage of various cellular \n mechanisms to gain entry into the cell after \n binding their specific cell surface receptors. \n • Some enveloped viruses undergo fusion, which \n fuses the viral envelope with the plasma \n membrane. \n • Both enveloped and non-enveloped viruses take \n advantage of receptor-mediated endocytosis in \n caveolin- or clathrin-coated pits to gain entry into \n the cytoplasm of the cell; still other viruses \n undergo receptor-mediated endocytosis that is \n independent of both clathrin and caveolin. \n • Bulk-phase endocytosis or phagocytosis are also \n utilized by viruses to gain entry into the cell.

Uncoating

* Release of the virus genome into the cell due to the breakdown or the removal of the capsid

Class I: dsDNA viruses examples:

* Adenoviridae→ Adenovirus
* Herpesviridae→ Herpes simplex virus, Epstein-Barr virus, varicella zoster virus
* Papillomaviridae→ Human papillomavirus
* Polymomaviridae→ JC polyomavirus, BK polyomavirus, SV 40
* Poxviridae→ Variola, Vaccinia

Class I: dsDNA viruses

• All living organisms have dsDNA genomes and use DNA polymerases to \n copy their genomes and RNA polymerases to transcribe their genes \n • All dsDNA viruses that infect humans enter the nucleus of the cell to use \n some aspect of the host machinery \n • The exception are the poxviruses, which encode all the proteins they need \n for both transcription and genome replication (and so do not require entry \n into the nucleus) \n • Herpesviruses, adenoviruses, polyomaviruses, papillomaviruses, poxviruses

Class II: ssDNA viruses

• ssDNA viruses primarily infect bacteria and plants \n • Anelloviridae and Parvoviridae infect humans \n • Non–enveloped isosahedral capsids, 18-30 nm in diameter \n • Very small genomes (4-6 kb) and are completely dependent on host \n cells enzymes for genome replication and transcription

Class II: ssDNA viruses Examples:

* Parvoviridae→ Parvovirus B19
* Anellovridae→Torque teno virus

Class III: dsRNA viruses

• Non-enveloped with iscosahedral capsids and segmented genomes \n • Reoviridae and Picobirnaviridae infect humans

• RNA viruses do not enter the nucleus of an infected cell \n • Without a DNA intermediate, they do not use any of the cell’s DNA replication \n machinery \n • RNA viruses must transcribe their genes, however \n • Use a viral RNA-dependent RNA polymerase (RdRp) \n • Brought within the virion so transcription can occur immediately

Class III: dsRNA viruses Examples:

* Picobirnaviridae→ Human picobirnavirus
* Reoviridae→ Rotavirus

Class IV: +ssRNA viruses

When RNA is single-stranded, it can consist of either \n strand of a complementary double-stranded molecule \n of nucleic acid \n • Positive-sense RNA (+ssRNA) acts as mRNA (is \n translatable by ribosomes) \n • Also known as “positive-strand” or “positive-sense” \n RNA \n • Negative-sense RNA (-ssRNA) is not translatable and \n must first be transcribed into positive-sense RNA by \n an RNA-dependent RNA polymerase (RdRp) \n • Also known as “negative-strand” or “negative-sense” \n RNA \n • Because +ssRNA viruses have genomes that can \n immediately be translated by ribosomes, they have \n infectious genomes \n • +ssRNA genomes have IRES sequences or become \n capped and polyadenylated so they can be directly \n translated upon entry into a cell

Class IV: +ssRNA viruses Examples:

* Astroviridae→ Human astrovirus
* Caliciviridae→ Norwalk virus
* Coronaviridae→ Human coronavirus
* Flaviviridae→ Dengue virus, yellow fever virus, West Nile virus, hepatitus C virus.
* Hepeviridae→ Hepatitis E virus
* Picornaviridae→ Poliovirus, rhinovirus, enterovirus, hepatitis A virus
* Togaviridae→ Eastern equine encephalitis, Chikungunya virus, rubella virus

Class V: -ssRNA viruses

• -ssRNA genomes do not act as mRNA, so these viruses must carry an RdRp \n within the virion (as the dsRNA viruses do) \n • Transcription of viral mRNAs is first event following uncoating

• Generally do not enter the nucleus (influenza viruses are an exception) \n • Are enveloped \n • Are segmented (influenza virus) or non-segmented (Ebola virus, rabies \n virus) \n • Possess helical nucleocapsids: -ssRNA viral genome is coated by a \n repeating nucleocapsid protein (termed NP or N)

Class V: -ssRNA viruses Examples:

* Arenaviridae→ Lymphocytic choriomeningitis virus, Lassa virus, Machupo virus
* Bunyaviridae→ Hantavirus, Crimean-Congo hemorrhagic fever virus
* Filoviridae→ Ebola virus, Marburg virus
* Orthomyxoviridae→ Influenza A virus, Influenza B virus
* Paramyxoviridae→ Nipah virus, Hendra virus, measles virus, mumps virus
* Rhabdoviridae→ Rabies virus

Class V: -ssRNA viruses (Ambisense viruses)

• Ambisense viruses have genomes that are partially positive-sense and \n partially negative-sense \n • Arenaviruses (such as Lassa virus or lymphocytic choriomeningitis \n virus) \n • Ambisense viruses are still considered with -ssRNA viruses because \n the positive-sense portion of their genomes is not directly \n translatable

RNA viruses are more prone to mutation than DNA viruses, Why?

• DNA-dependent DNA polymerases have proofreading ability: they can remove \n an incorrectly placed nucleotide and replace it with the correct one. \n • RNA-dependent RNA polymerases do not have proofreading ability \n • Raises the overall error rate of the enzyme, from 1 error per 109 bases for a \n DNA polymerase to greater than 1 error per 105 bases for an RdRp, which \n results in lower enzyme fidelity, or accuracy \n • RNA viruses have some of the highest mutation rates of all biological \n entities

Other means of introducing genetic diversity in RNA viruses

Recombination and reassortment

Recombination

* occurs during genome replication when the RdRp jumps from the genome template of one virus strain to the genome template of another strain that has infected the same cell \n • Creates a hybrid genome different from either parent strain \n • Occurs at random sequences or at complementary sequences when the two genome templates base pair with each other

Reassortment

* when two strains of the same segmented virus infect the same cell, the genome segments may become mixed when new virions are assembling \n • A large concern for influenza A virus, as will be discussed in Chapter 10

Class VI: RNA viruses that reverse transcribe

• Also known as retroviruses \n • Possess +ssRNA genomes (2 copies per virion) \n • +ssRNA is not infectious, however!

• Do not transcribe or translate their genome \n immediately upon entry into the cell; instead, they \n reverse transcribe it from RNA to dsDNA first \n • Carried out by reverse transcriptase \n • Followed by integration into a host chromosome \n • Cellular RNA polymerase II transcribes viral genes and \n the full-length +ssRNA genome \n • Assembly of new virions begins once genome has been \n replicated and viral proteins have been translated

Class VI: RNA viruses that reverse transcribe Examples:

* Retroviridae → Human immunodeficiency virus-1 and -2

Class VII: DNA viruses that reverse transcribe

• A retroid virus is the term for any virus that reverse transcribes, \n whether RNA or DNA \n • Two families of DNA viruses also undergo reverse transcription \n • Caulimoviridae (infects plants) and Hepadnaviridae (infects animals)

• Retroviruses use reverse transcriptase \n immediately upon entry into the cell to create \n cDNA that becomes integrated into a host \n chromosome

Class VII: DNA viruses that reverse transcribe Examples:

* Hepadnaviridae→ Hepatitus B virus

Assembly

* the construction of new \n virions composed of viral proteins \n and the replicated genome \n • Often occurs alongside maturation \n and/or release \n • Site depends upon the particular \n virus \n • Within the nucleus, at the plasma \n membrane, or at intracellular organelles \n (rER, Golgi complex, vesicles)

Maturation

* the final changes within an immature virion that result in an infectious virus particle
* Example: \n • Influenza hemagglutinin (HA) must be cleaved into HA1 and HA2 in order for \n the virion to become infectious \n • Carried out by cellular proteases

Virus release

**Release**: the escape of nascent virions from the infected cell \n • For enveloped viruses, release can occur \n through budding \n • Assembly occurs at a membrane within the \n cell, with virus attachment proteins \n becoming embedded into the membrane \n • Viral proteins facilitate the curving of the \n membrane until it becomes separated from \n the cell membrane, creating the viral \n envelope \n • Different viruses bud from the plasma \n membrane, rER, Golgi complex, or vesicles

Can also occur via: \n • Lysis of the cell \n • Exocytosis

• Budding

The development of ________________ is one of the most important functions of the adaptive immune system

immunological memory

Vaccination

* is the intentional inoculation of a person (or animal) with a harmless form of a pathogen \n • Activates the immune system, which generates a memory response \n • The immune system will be activated faster and to a greater \n magnitude upon any subsequent exposures to the virus \n • Vaccines and antivirals are tested extensively in cells, animals, and in \n clinical trials of human volunteers before they are approved for sale \n (marketing) to the general population \n Vaccine Development

The history of vaccination begins

* with variola virus, the cause of smallpox \n • Smallpox killed ∼30% of those it infected (500 million people in the 20 th century alone) \n • Ancient China: pulverized dried smallpox scabs were inhales or injected into uninfected \n people, known as variolation \n • Led to a milder form of the disease \n • 2-3% fatality rate \n • Infected individuals could transmit the infection to others \n History of Vaccination

country doctor Edward Jenner

* observed that milkmaids who contracted cowpox were protected from contracting smallpox \n • Collected the fluid from a cowpox sore on the hand of milkmaid Sarah Nelmes \n and injected it into a young boy, James Phipps \n • Phipps was protected from contracting the virus when exposed to people \n with smallpox \n - Jenner initiated larger-scale tests, which were successful \n - Jenner was not the first to attempt this vaccination, but he \n receives credit for promoting its wide-spread use and \n providing vaccine material to any that requested it

Louis Pasteur creates the second vaccine against viruses

• Pasteur and colleagues had discovered that the causative agent of \n rabies could be transmitted from dog to dog by transferring spinal \n cord and brain tissue into an uninfected dog \n • They infected rabbits with the infected tissue and removed their \n spinal cords, which were dried and used as a successful vaccine in \n dogs \n • First tested on a 9-year old child, Joseph Meister, who had been \n bitten 14 times by a rabid dog \n • Meister lived, and of the 350 people treated with the vaccine in the \n following year, only 1 child died (who had been bitten 6 days before \n receiving the vaccination)

First viruses were created from____________ -- the only way \n known to propagate viruses at the time

infected animal tissues

Alice Miles Woodruff and Ernest Goodpasture discovered____

* that embryonated hen’s eggs would support the growth of fowlpox virus and other viruses \n • Used to create vaccines against \n influenza virus in 1945 and \n yellow fever virus in 1935 \n • Still the standard method of \n propagating virus for the yearly \n influenza vaccine \n • Reason why those allergic to eggs \n cannot receive the standard \n influenza vaccine \n Cell culture advances replaced \n this technique in the 1960s

An effective vaccine must be ____________

* immunogenic

• Vaccines must activate the innate and adaptive arms of the immune system \n • Most vaccines rely upon activating the humoral response, the production of \n antibodies that can neutralize viruses \n • For protection against other viruses, the cell-mediated response involving T \n cells must be activated \n • Knowledge of the virus, its pathogenicity, and how the immune system \n effectively responds against it is helpful in designing an effective vaccine \n • Many vaccines contain an adjuvant that boosts the immunogenicity of the \n vaccine material \n • Sequester the antigen in the tissue for longer, allowing more time for \n endocytosis by dendritic cells \n • Molecules that activate pattern recognition receptors

Live attenuated virus (current use)

* composed of infectious virus that has been attenuated (weakened) so it no longer replicates efficiently in humans \n

• Rule of thumb for vaccine development: the more similar a vaccine is to the \n pathogenic virus, the better the immunological response will be \n • Live attenuated virus vaccines are considered to provide the most \n biologically relevant immunity

Live attenuated virus Limitation

• Usually require refrigeration to remain immunogenic \n • Possibility exists that the attenuated virus could revert back to a wild-type strain that is fully virulent \n • Therefore not recommended for immunocompromised individuals \n

Inactivated virus vaccines (current use)

* virus is completely inactivated by high heat or low amounts of formaldehyde \n • Can be used without fear of reversion to a wild-type strain \n • Do not usually require refrigeration \n • Can be transported easily in a lyophilized (freeze-dried) form

Inactivated virus vaccines Limitations:

• Some viruses are not immunogenic following inactivation \n • “Booster” shots may be required to maintain immunity against the virus \n • Inactivation can (very rarely) modify viral proteins to create a pro- \n inflammatory response against the pathogen \n • An inactivated vaccine against respiratory syncytial virus resulted \n in worse symptoms when the vaccinated children were infected

Recombinant subunit vaccines (current use)

* use gene cloning and recombinant protein expression systems to produce large amounts of viral proteins (subunits) that are used as the vaccine material

• Can be created for viruses that are not easily propagated, as long as DNA \n sequence is available \n • No concern of infection, reversion, or improper inactivation

Recombinant subunit vaccines Limitations:

• Frequently requires booster shots, since only 1 or a few different \n subunits are used in the formulation, rather than the entire virus \n • Expensive \n • Requires specialized laboratories and expertise

mRNA vaccines (current use)

* use lipid nanoparticles to deliver mRNA into cells, which is translated into \n viral proteins by the cell’s ribosomes.

• Vaccine can be formulated quickly \n • Can be used for viruses not able to be propagated in culture, as long as \n virus genome sequences are available \n • No concern of infection, reversion, or improper inactivation

mRNA vaccines Limitation:

• Frequently requires booster shots, since only one viral protein is \n expressed \n • mRNA must be translated by ribosomes into the viral protein in order \n to be immunogenic \n • May not be fully immunogenic if target viral protein mutates \n • Requires specialized laboratories and expertise \n • Can be expensive to manufacture \n • Must be kept frozen at -20°C or -80°C, making distribution difficult in \n some areas of the world \n Types of Current Vaccines

Vaccine use in viruses:

a

The MMR vaccine _________ cause autism!

does not

DNA vaccines

* deliver viral DNA directly into the cells of an individual \n • Within the cells, the viral gene is expressed into the viral protein to which \n the host immune system responds \n • DNA is injected into cells via particle bombardment, a needle-free \n compressed air system, electroporation, or lipid nanoparticles \n • Still in clinical trial stages of testing for humans \n • West Nile virus, influenza virus, HPV, HBV, HIV, dengue virus \n **• Prime-boost strategy is often necessary**: DNA vaccine is followed by a \n booster shot with another type of vaccine to supplement the \n immunogenicity against the virus.
* Approved in used of horse.

Recombinant vector vaccines

* an attenuated or harmless virus is modified to include DNA that encodes the viral antigen of interest \n • Like a DNA vaccine, except that a virus \n is used to deliver the gene, rather \n than a DNA plasmid \n • Commonly used vectors: adenovirus \n strains, poxviruses (canarypox or \n vaccinia virus), retroviruses, \n lentiviruses (a type of retrovirus that \n can replicate in non-dividing cells) \n • Vectors can be modified to create \n replication-defective viruses that can \n infect cells but cannot replicate within \n them.

• Have been approved as a rabies vaccine for wild animals

Viral vaccines used in humans:

a

Active immunity

generation of memory cells by a person’s immune system

Passive immunity

* transfer of immune system components, primarily antibodies (immunoglobulins), into a person \n • Active immunity generates cells that can be later activated, but passive \n immunity transfers antibody that will eventually be removed from the system \n → temporary fix

_____________ interfere with one of the stages of viral replication

Antivirals

Inhibiting Attachment, Penetration, Uncoating

• Inhibitors of viral attachment and entry are biologically the optimal way to \n inhibit viral replication \n • No entry = no replication = no provirus integration or mutations that could \n translate into drug resistance

Only a few inhibitors of attachment, penetration, and uncoating exist:

• Maraviroc: inhibits binding of HIV-1 to one of its co-receptors, CCR5 \n • Does not inhibit binding to CXCR4, another HIV co-receptor \n • Is not effective in people infected with CCR5- and CXCR4-tropic strains \n • Enfuvirtide: binds to the HIV protein that fuses the viral envelope with the \n plasma membrane of the cell \n • Docosanol: inhibits fusion of HSV-1 envelope with plasma membrane \n • Amantadine and rimantadine: inhibit the M2 protein, thereby preventing \n the influenza envelope from fusing with the endosome

Inhibiting Genome Replication

• The greatest number of antiviral drugs available interfere with genome \n replication \n • The great majority of these interfere with retroid viruses, namely HIB and HBV

• Nucleoside analogs: a class of small molecule drugs that terminate reverse \n transcription \n • Known as nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) \n when used to prevent reverse transcription \n • NRTIs available that function as competitive analogs of adenine, thymine, \n cytosine, guanine, and uracil

Inhibiting Assembly, Maturation, and Release

• No antivirals exist that inhibit assembly \n • Since the nucleocapsid or capsid proteins are often very numerous, this \n would require a high concentration of drug to be effective \n • Since maturation results in an infectious virion, it is a potential drug target: \n • HIV protease, which facilitates maturation, is blocked by several protease \n inhibitors \n • Release is a drug target if viral proteins facilitate the process \n • Influenza A virus neuraminidase cleaves sialic acids from budding virions \n and the surface of the cell to prevent the attachment of new virions to the \n same cell \n • Oseltamivir, zanamivir, and peramivir are neuraminidase inhibitors

Boosting the immune response

• Most antivirals are specific for one or only closely-related viruses \n • Another approach is to develop drugs that boost the immune response \n • Type 1 interferons produce an anti-viral state within cells through activation of \n PKR and OAS/RNase L pathways \n • IFN-a is useful alone or in combination for chronic hepatitis C infection \n • Produced through recombinant protein expression systems \n • Type 1 IFNs have pleotropic outcomes upon several immune cell types, so \n off-target effects may occur

__________________is the process of modifying an individual’s DNA for \n therapeutic purposes

Gene therapy

_____________ (serotype 5) are the most common virus used for gene \n therapy thus far

Adenoviruses

_________ are derived from normal human cells that have lost \n proper regulation of the cell cycle, leading to uncontrolled proliferation \n of cells that invade nearby tissues

Cancerous cells

______________is a disease caused by uncontrolled cell division that leads to a \n growth of cells that invade nearby tissues and spread to other areas of \n the body

Cancer

benign

tumor (mass of cells) stops dividing once it reaches a certain size

malignant

tumor invades nearby tissues due to mutations

The tumor acquires mutations that lead to __________, the growth of \n new blood vessels, in order to better feed the tumor

angiogenesis

Metastasis

the tumor cells spread to other locations in the body

Carcinogens

are substances that induce mutations in DNA that may lead to the development of a cancerous cell

Physical carcinogen

ionizing radiation or ultraviolet light