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Viruses Chapter 33 Roadmap. - PPT Presentation

2017 Pearson Education Inc Introduction A virus is an obligate intracellular parasite Viruses enter a host cell and use the host s biosynthetic machinery to reproduce and synthesize its proteins ID: 726304

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Slide1

VirusesSlide2

Chapter 33 Roadmap.

© 2017 Pearson Education, Inc.Slide3

Introduction

A

virus is an obligate, intracellular parasite Viruses enter a host

cell

and use the host’

s biosynthetic machinery to reproduce and synthesize its proteins

Most biologists would argue that viruses are not alive, because they depend on their host cell to satisfy the key attributes of lifeSlide4

Introduction

Viruses

Have a genomeAre well adaptedEvolve Nearly all organisms examined thus far are parasitized by at least one kind of virusSlide5

Table 33.1

© 2017 Pearson Education, Inc.Slide6

Why Do Biologists Study Viruses?

The enormous diversity of potential host cells has resulted in the evolution of an equally diverse assortment of viruses

Do viruses contribute to organismal evolution?Slide7

Viruses Shape the Evolution of Organisms

Viruses have promoted evolution of organismal traits

Physical barriers and immune defenses that reduce the occurrence or impact of infectionViruses have also directly influenced the genetic makeup of organisms

Lateral gene transfer

—introduce foreign genes into cellular genomes by picking up genes from one organism and shuttling them to anotherSlide8

Viruses Shape the Evolution of Organisms

Viruses also contribute their own genetic material to organisms

From 5% to 8% of the human genome consists of remnants of viral genomes from past infectionsSome viral genes are part of what makes us human

A protein encoded by an abandoned viral gene is necessary for development and function of placentaSlide9

Figure 33.1

Central nervous system

dengue virus

polio virus

rabies virus

West Nile virus

Lymphatic and

immune systems

Epstein-Barr virus

HIV

measles virus

Trachea and lungs

adenovirus

influenza virus

SARS-CoV

Heart

Coxsackie virus

Liver and digestive tract

dengue virus

Ebola virus

hepatitis A, B, C, D, E

viruses

rotavirus

yellow fever virus

Blood vessels and

blood cells

Ebola virus

hantavirus

Reproductive organs

herpes simplex 2 virus

papillomavirus

Skin

herpes simplex 1 virus

measles virus

papillomavirusrubella virussmallpox virusvaricella zoster virus

Peripheral nerves

rabies virusvaricella zoster virus

© 2017 Pearson Education, Inc.Slide10

Viruses Cause Disease

An

epidemic is a disease that rapidly infects a large number of individuals over a widening area Viruses have caused the most devastating epidemics in recent human history

A

pandemic

is a worldwide epidemic

The

Spanish flu

outbreak of 1918–1919 was the most devastating pandemic to date

The strain of influenza virus that emerged in 1918 was particularly

virulent

(it tended to cause severe disease)

Worldwide, the Spanish flu killed up to 50 million peopleSlide11

Figure 33.2

(a)

Deadly impact of the 1918 influenza pandemic

Life expectancy (years)

This downward spike is due

to the 1918 flu epidemic

Year

(b)

Emergency hospital at the start of the 1918 pandemic

© 2017 Pearson Education, Inc.Slide12

Current Viral Pandemics in Humans: AIDS

Human immunodeficiency virus

(HIV) causes acquired immune deficiency syndrome

(

AIDS

)

AIDS has surpassed the 1918–1919 influenza,

as well as

measles, and smallpox epidemics, in its impact on humansSlide13

How Does HIV Cause AIDS?

HIV parasitizes and destroys cells called

helper T cells of the immune system, the body

s defense system against disease

During HIV infection, the total number of helper T cells in the blood gradually declines

The number of T cells the body manufactures cannot keep up with the number of T cells the virus destroysSlide14

Figure 33.3

Helper T cells per mm

3

blood

Acute

phase

Weeks

Rapid

decline

Chronic phase

AIDS

Gradual decline

Years

© 2017 Pearson Education, Inc.Slide15

How Does HIV Cause AIDS?

When the T-cell count drops, the immune system’

s responses to invading bacteria and viruses become less and less effectiveHIV kills people indirectly—it makes them susceptible to pneumonia, parasites, and unusual types of cancer

Slide16

What Is the Scope of the AIDS Pandemic?

AIDS has already killed 36 million people worldwide

The highest rates of infection in sub-saharan Africa

23% of the Botswana population is HIV positive

There are about 34 million HIV-infected people worldwide

An additional 2.3 million people are infected

each year

Because HIV is primarily a sexually transmitted virus, it disproportionately affects young adultsSlide17

How Do Biologists Study Viruses?

Researchers who study viruses usually focus on how to prevent or reduce the effects of the diseases that they cause

To treat viral infections, need to identify virus specific targets and then use

Vaccines—activate the immune system against the targets

Antiviral drugs—directly interfere with viral replicationSlide18

How Do Biologists Study Viruses?

The first step in studying a virus is to isolate it, which takes researchers into the realm of

nanobiologyStructures are measured in billionths of a meter—

1 nanometer (nm) is 10

–9

meter

Viruses range in size from only about 20 to 300 nm in diameter

Viruses are tiny relative to eukaryotic or even bacterial cellsSlide19

Figure 33.4

Eukaryotic cell

(human red blood cell)

7

µ

m

Bacterial cell

(

E. coli

)

2

µ

m

0.1

µ

m

Virus particles

(HIV)

© 2017 Pearson Education, Inc.Slide20

How Do Biologists Study Viruses?

Researchers use Koch’

s postulates to isolate a virus and confirm that it is the causative agent of infectionOnce a virus is isolated, biologists analyze

The structure of the

virion

The nature of the genetic material that is transmitted from one host to another

Mechanism by which the virus replicatesSlide21

Analyzing Morphological Traits

In terms of overall structure, most viruses fall into just two general categories:

Those enclosed only by a protein shell called a capsid

Those

enclosed by both a capsid

and one or more membranous

envelopesSlide22

Analyzing Morphological Traits

Most viruses produce

virions with helical or icosahedral capsidsSome viruses have more complex capsid shapesThe capsid serves two functions:

Protects the genome while outside the host

Releases the genome when infecting a new cell Slide23

Figure 33.5

(a)

Tobacco mosaic virus

(b)

Adenovirus

(c)

Bacteriophage T4

(d)

Smallpox virus

50 nm

100 nm

100 nm

Genome

Protein capsid

Genome

Protein capsid

Genome

Genome

Protein capsid

Protein

capsid

Membranous envelopes

50 nm

© 2017 Pearson Education, Inc.Slide24

Analyzing the Genetic Material

In addition to morphology, viruses can be categorized based on the nature of their genome

Many viruses break the central dogma of molecular biologyInformation flows from DNA →

mRNA → proteinsSlide25

Analyzing the Genetic Material

There is a wide diversity of viral genome types

They may consist of DNA or RNAThey may be linear or circularThey may consist of a single molecule or have several different segments

They may be single stranded or double strandedSlide26

Analyzing the Genetic Material

Single-stranded RNA genomes can be classified as

Positive-sense virusesThe genome contains the same sequences as the mRNA required to produce viral proteins

Negative-sense viruses

The base sequences in the genome are complementary to those in viral mRNAs

Ambisense

viruses

Contain one positive-sense region and one

negative-sense regionSlide27

Analyzing the Genetic Material

Viruses infect their host cells in one of two ways:

Via replicative growth

Produces the next generation of

virions

Often kills the host cell

In a dormant manner

Suspends

virion

production

Allows the virus to coexist with the host for a period

of timeSlide28

Analyzing the Phases of Replicative Growth

Six phases are common to replicative growth in virtually all viruses:

Attachment to a host cell and entry into the cytosol

Viral genome transcription and viral protein production

Viral genome replication

Assembly of a new generation of

virions

Exit from the infected cell

Transmission to a new hostSlide29

Analyzing the Phases of Replicative Growth

A

bacteriophage is a virus that infects bacterial cellsReplicative growth of a bacteriophage is called the lytic cycle

It ends with lysis (destruction) of the cell

In a single cycle, one virus can produce many progeny

The capacity of a bacteriophage to replicate results in nonlinear growthSlide30

Figure 33.6

Virion

Host-cell

genome

DNA mRNA Protein

1.

Viral genome enters host cell.

2.

Viral genome

is transcribed; viral

proteins are produced.

DNA

Protein

6.

Free

virions

in tissue or

environment

are transmitted

to new host.

3. Viral genome is replicated.

5.

Particles exit to exterior.

4.

Particles assemble inside host.

© 2017 Pearson Education, Inc.Slide31

Figure 33.7

Number of cells or viruses

Production of

bacteriophage

Division of cells

Time (minutes)

© 2017 Pearson Education, Inc.Slide32

How Do Viruses Enter a Cell?

The replicative cycle of a virus begins when a free

virion enters a target cellMost plant viruses are inserted directly into the host cell when a sucking insect has disrupted the cell wall

Viruses that parasitize bacterial or animal cells gain entry by binding to a specific molecule on the cell wall or plasma membrane

The viral genome can then be uncoated

At the cell surface

In the endosome Slide33

How Do Viruses Enter a Cell?

Research showed that HIV particles can enter cells only if the

virions bind to a membrane protein called CD4

The hypothesis was that CD4 functions as the receptor for HIV attachment

Researchers predicted that if CD4 is blocked, then HIV will not be able to enter host cells

Experimental tests supported this hypothesis

CD4

antibodies

blocked HIV from binding to and entering the T cell

Only cells with CD4 on their surface can be infected by HIVSlide34

Figure 33.8

HIV uses CD4 as the receptor to enter helper T cells.

Thus, only cells with free, unbound CD4 on their surface can be

infected by HIV.

HIV

Antibody

CD4

protein

Other proteins:

CD4:

Many cells infected No cells infected

1. Start with helper T cells.

2. Add antibodies

to block one

membrane protein in each sample.

3. Add HIV.

×160

Antibody to

protein

other than

CD4

Antibody

to CD4

Add

HIV

Add

HIV

CD4 is the membrane protein HIV uses to enter cells.

CD4 is not the membrane protein HIV uses to

enter cells. Does CD4 protein function as the

receptor that HIV uses to enter host cells? HIV will not infect cells with antibody to CD4 but will

infect other cells.

HIV will infect cells withantibody to CD4.

© 2017 Pearson Education, Inc.Slide35

How Do Viruses Enter a Cell?

HIV virions can enter cells only if the virions bind not only to CD4 but also to a second membrane protein, called a

co-receptorWhen the proteins in a virion’

s envelope bind to both receptors:

The lipid bilayers of the particle

s envelope and the plasma membrane of the helper T cell fuse

The viral capsid enters the cytoplasm and infection proceedsSlide36

Figure 33.9a

HIV

CD4

Immune

system cell

Co-receptor

2.

HIV’s envelope protein binds

to CD4 and a co-receptor.

3.

The binding event causes

the membranes to fuse,

allowing the viral capsid to

enter the host cell and start

an infection cycle.

1.

Both HIV particles and

human immune cells have

specialized proteins in their

membranes (just some of

the proteins are shown).

© 2017 Pearson Education, Inc.Slide37

How Do Viruses Enter a Cell?

When the virus is uncoated in the endosome, it is first internalized into the host cell via endocytosis

The endosome vesicle that engulfs the virion acidifies, changing the viral attachment proteinsThese proteins promote fusion of the viral envelope and the endosomal membraneSlide38

Figure 33.9b

H

+

Endosome

Influenza

H

+

Animal cell

H

+

H

+

1.

Influenza’s envelope proteins

attach to a common carbohydrate

found on animal cells, inducing

virion

uptake via endocytosis.

2.

Protons are pumped into

the endosome, causing the

envelope proteins to change

shape.

3.

The envelope and endosome

membranes are brought together

and eventually fuse, releasing the

viral genome into the cytoplasm.

© 2017 Pearson Education, Inc.Slide39

How Do Viruses Enter a Cell?

Researchers are searching for compounds that block attachment and uncoating of viruses

Drugs that interfere with viral infection or replication are called antiviralsSlide40

How Do Viruses Produce Proteins?

In all viruses, translation of viral transcripts depends entirely on the host

Viruses lack ribosomes, amino acids, ATP, and most of the other biosynthetic machinery required for translationSlide41

How Do Viruses Produce Proteins?

Viral mRNAs that code for envelope proteins are

Translated as if they were mRNAs for the cell’s own membrane proteinsmRNAs that code for capsid proteins are

Translated by free cytosolic ribosomes as if they were cellular mRNAs for cytosolic proteinsSlide42

How Do Viruses Produce Proteins?

In some viruses, long polypeptides called

polyproteins are cut into functional proteins by a viral proteaseThe discovery that HIV produces a protease triggered a search for drugs that would inhibit the enzyme

Several HIV protease inhibitors are currently

being used to interfere with viral replicationSlide43

Figure 33.10

(a)

HIV’s protease enzyme

(b)

Could a drug block the active site?

Protease

inhibitor

Active site

of protease

© 2017 Pearson Education, Inc.Slide44

How Do Viruses Copy Their Genomes?

In addition to transcription and translation, viruses must also copy their genetic material to make a new generation of virions

They depend on the host cell for nucleotide monomersSome DNA viruses depend on the host-cell DNA polymerase machinery to replicate their genomesSlide45

How Do Viruses Copy Their Genomes?

Viruses with an RNA genome must supply their own enzyme to make copies of their genome

Most RNA viruses use an RNA polymerase called RNA replicase, which synthesizes RNA from an

RNA template

Synthesis uses ribonucleotides provided by the

host cellSlide46

Figure 33.11

(+)

ssRNA

Replicase

Genomic strand

dsRNA intermediate

Template strand

Replicase

(+)ssRNA products

(genome copies)

© 2017 Pearson Education, Inc.Slide47

How Do Viruses Copy Their Genomes?

Some RNA viruses, such as HIV, are

retroviruses

In retroviruses, the RNA genome is transcribed to DNA by a viral enzyme called

reverse transcriptase

Reverse transcriptase is a DNA polymerase that

Makes a single-stranded

complementary DNA

(

cDNA

) from a single-stranded RNA template

Removes the RNA strand and synthesizes the complementary DNA strand, resulting in double-stranded DNA

The

cDNA

copy of the genome is then inserted by a viral protein into the host-cell chromosomeSlide48

Figure 33.12

cDNA

RNA template

First, reverse transcriptase

synthesizes

cDNA

from RNA

Double-stranded cDNA

cDNA

template

Then, reverse transcriptase

synthesizes double-stranded

DNA from cDNA

© 2017 Pearson Education, Inc.Slide49

How Are New Virions Assembled?

During assembly, viral genomes are packaged into capsids

Some viruses also include copies of non-capsid proteins inside the capsidThe assembly process is not yet well understoodSome viruses assemble the capsid first and then use motor proteins to pull the viral genome inside

Other viruses assemble the capsid around the genomic materialSlide50

How Are New Virions Assembled?

Enveloped viruses use the host endomembrane system to transport their envelope proteins to the appropriate membrane for assemblySlide51

How Do Progeny Virions Exit an Infected Cell?

Most viruses leave a host cell in one of two ways:

Enveloped viruses bud from a cell through the cell membrane

They take part of the cell membrane with them, including envelope proteins that were inserted into the membrane

Nonenveloped

viruses burst out of the cell

Release their

virions

from the cell by lysing it—commonly referred to as the burst

Bacteriophages produce lytic enzymes that break down host-cell wallSlide52

Figure 33.13

(a)

An enveloped virus budding from a host cell

Cell interior

Cell exterior

Protease

activity

Viral core

Viral envelope proteins

(b)

Nonenveloped

viruses bursting from a host cell

Cell wall

Virions

escape

from lysed cell

Plasma membrane

50 nm

500 nm

© 2017 Pearson Education, Inc.Slide53

How Are Virions Transmitted to New Hosts?

A new replicative cycle begins when the virions infect new cells—either within the same organism or in another organism

A virus’s long-term success depends on its ability to be transmitted through the environment from one individual to another

Natural selection thus favors viral alleles that allow the virus to

Replicate within a host

Be transmitted to new hostsSlide54

Analyzing How Viruses Coexist with Host Cells

All viruses undergo replicative growth, but some can arrest the replicative cycle and enter a dormant state

In bacteriophages, this alternate type of infection is called lysogeny

No virions are produced during lysogeny

However, the host

s DNA polymerase replicates the viral DNA each time the cell divides

Molecular cues from the host cell can direct the virus toward lysogeny or the lytic cycleSlide55

Figure 33.14

Infection

Integration

Replication

of genome

4.

Cell divides. Viral genome is

transmitted to daughter cells.

OR

DNA mRNA Protein

1.

Viral genome

enters host cell.

2.

Viral genome

integrates into host-

cell genome.

3.

Host-cell DNA

polymerase copies

chromosome.

At any point after integration,

the virus may activate the

replicative cycle.

© 2017 Pearson Education, Inc.Slide56

Analyzing How Viruses Coexist with Host Cells

In viruses that infect animal cells, the dormant state is called

latency HIV has a latency periodViral genes are not expressed until the helper T cell host is activated by the immune responseSlide57

What Themes Occur in the Diversification of Viruses?

Mutation and natural selection guarantee that viral genomes will continually adapt to their hosts

’ defensesBecause most viral polymerases have high error rates and viruses lack error repair enzymes, mutation rates are extremely high

Many viruses change constantly—giving them the potential to evolve rapidlySlide58

Where Did Viruses Come From?

Nobody knows how viruses originated

Biologists are considering three hypotheses to explain the origin of viruses:Origin in plasmids and transposable elements?

Origin in symbiotic bacteria?

Origin at the origin of life?Slide59

Origin in Plasmids and Transposable Elements?

Hypothesis: Simple viruses are “

escaped gene sets” Mobile genetic elements descended from genes that escaped from prokaryotic or eukaryotic chromosomes

Escaped gene sets encode information needed to replicate themselves at expense of genomes that once held them

Included instructions for making a capsid

Evidence: Discovered virus recently derived from intact prokaryotic or eukaryotic genes, and viral genome still strongly resembled those genesSlide60

Origin in Symbiotic Bacteria?

Hypothesis: DNA viruses descend from free-living bacteria that lived inside eukaryotic cells

The bacteria gradually degenerated into viruses Slowly lost genes needed to synthesize ATP, nucleic acids, amino acids, and other compoundsEvidence to support: Discovery of a cell that possesses a genome similar to that of a large DNA virusSlide61

Origin at the Origin of Life?

Hypothesis: Viruses descended from the first RNA-based life-forms on Earth

Evidence to support: Ubiquity of viruses suggests that they have been evolving along with organisms since life beganSeveral proteins commonly expressed in many viruses are not expressed in any known cell

Genes coding for these proteins may have come from an RNA-world pool of genes instead of a cellSlide62

Emerging Viruses, Emerging Diseases

Although it is not known how the various types of viruses originated, it is certain that viruses will continue to diversify

HIV is an example of a virus responsible for an emerging disease

New illnesses that suddenly affect significant numbers of individuals in a host population

The causative agents are considered to be emerging viruses

They switched from their traditional host species to a new host—humansSlide63

Some Emerging Viruses Arise from Genome Reassortment

Influenza vaccines are updated annually because of small changes that arise from the virus

’s error-prone RNA replicaseHowever, influenza can also acquire alleles that are entirely new to the

strain

A virus strain consists of populations that have similar characteristicsSlide64

Some Emerging Viruses Arise from Genome Reassortment

Influenza has a single-stranded RNA genome consisting of eight segments

Most segments encode only one proteinIf two viruses infect the same cell, replicated genomic segments are randomly shuffled

Progeny often have segments from each parent virusSlide65

Figure 33.15

Influenza

Host cell

Recombinant

strain

1.

Two different strains of

influenza infect the same cell.

2.

Replication produces a

mix of strain-specific genomic

segments in host cytoplasm.

3.

Reassortment

of genomic

segments generates new,

recombinant strains.

© 2017 Pearson Education, Inc.Slide66

Using Phylogenetic Trees to Understand Emerging Viruses

Researchers analyze a virus’

s evolutionary history to determine if an emerging virus has jumped to a new hostFor example, analyzing the phylogenetic tree for HIV reveals three findings:

There are

siminan

immunodeficiency viruses

There are two distinct types of human HIV

HIV-1 and HIV-2

Multiple

jumps

have occurred

There are several strains of HIV-1, suggesting that it has jumped between species several timesSlide67

Figure 33.16

HIV strains that infect humans

HIV strains that infect other primates

SIV-Sykes monkey

SIV-sooty

mangabey

HIV-2

SIVs from four

monkey species

SIV-chimp strain cpzTAN1

HIV-1 strain O

(“O” stands for outlier)

SIV-chimp strain

cpzUS

HIV-1 strain N

(“N” stands for new;

discovered recently)

HIV-1 strain M

(“M” stands for main

strain responsible for

the AIDS epidemic)

© 2017 Pearson Education, Inc.Slide68

Responding to a Virus Outbreak

A virus outbreak is indicated by a large number of patients:

With identical and unusual disease symptoms In the same geographic area Over a short period of time

Physicians report these cases to public health officialsSlide69

Responding to a Virus Outbreak

Public health officials

Identify the agent that is causing the new illness

Identify the origin of the outbreakSlide70

Responding to a Virus Outbreak

In 2002, outbreak of an unknown respiratory

syndrome started in southern China and spread to several countries across the globe, causing over 8000 probable infections and killing 774 people Illness became known as severe acute respiratory syndrome (SARS)

Caused by a new coronavirus

Genome of SARS-

CoV

was rapidly sequenced

Source of the outbreak still had to be determinedSlide71

Responding to a Virus Outbreak

Epidemiologists had to decide how patients acquired the virus

Horseshoe bat is the natural host (reservoir)Virus also identified in the civet, a small mammal commonly sold in markets in southern China

This observation provided link between bats and human outbreakSlide72

Key Lineages of Viruses

Because scientists are almost certain that viruses originated multiple times, there is no such thing as the phylogeny of all viruses

To organize the diversity of viruses, researchers use the Baltimore classification system:Viruses are grouped into seven general categories based on the nature of their genetic material and how they replicateSlide73

Figure 33.17

DNA viruses

Class I

dsDNA

Class II

ssDNA

Class III

dsRNA

RNA viruses

Class IV

(+)ssRNA

Class V

(–)ssRNA

Reverse-transcribing viruses

Class VI

(+)ssRNA (RT)

Reverse

transcription

Reverse

transcription

Class VII

dsDNA (RT)

mRNA

To viral mRNA and proteins

Genome replication

Proteins

© 2017 Pearson Education, Inc.Slide74

Key Lineages of Viruses

Within the Baltimore classification system, about 100 virus families are distinguished by

Virion and genome morphology

The nature of the host species

How the virus replicates within the hostSlide75

Table 33.2

© 2017 Pearson Education, Inc.Slide76

Double-Stranded DNA (dsDNA) Viruses

Smallpox

Eradicated by worldwide vaccination programsHuman papilloma virus (HPV), herpesviruses, and adenoviruses

Viruses like HPV can induce host cells to enter S phase despite absence of normal growth signals

This ability may be responsible for the proposed link between HPV infections and cervical cancerSlide77

Single-Stranded DNA (ssDNA) Viruses

Canine parvovirus type 2

Causes a fatal disease in dogs if untreatedRare in domesticated dogs due to vaccineDensovirus

Triggered an epidemic of wasting disease in sea stars that is decimating populations from Baja California to southern AlaskaSlide78

Table 33.3

© 2017 Pearson Education, Inc.Slide79

Double-Stranded RNA (dsRNA) Viruses

Many diseases in rice, corn, sugarcane, and other crops are caused by

dsRNA virusesThe bluetongue virusCauses a deadly disease that has significantly affected the livestock industry

Reovirus

and rotavirus

Infections are leading cause of infant diarrheaSlide80

Positive-Sense Single-Stranded RNA

([+]ssRNA

) VirusesMost of the commercially important plant viruses belong to this group

Members of this group also

Parasitize bacteria, fungi, and animals

Include the viruses that cause the common cold, polio, SARS-

CoV

, West Nile virus, and hepatitis in humansSlide81

Negative-Sense Single-Stranded RNA

([–]ssRNA

) VirusesA wide variety of plants and animals are parasitized by viruses that have (–)

ssRNA

genomes

Flu, mumps, and measles

Ebola virusSlide82

Table 33.4

© 2017 Pearson Education, Inc.Slide83

Reverse-Transcribing

(+)ssRNA Viruses

Rous sarcoma virus (chickens), mouse mammary tumor virus, and murine (mouse) leukemia virus

Contribute to the development of cancer

HIVSlide84

Reverse-Transcribing dsDNA Viruses

Hepatitis B virus

About 5% of adults infected with HBV have a chronic infection that has been linked to the development of liver cancer