Transcript HIV-1

Viruses: genetic elements encased in
protein
• Viruses cannot reproduce independently: they are missing
several of the characteristics of living organisms (no cellular
organization, no growth, no independent replication).
• They do cause human diseases such as influenza, polio,
smallpox, and AIDS.
• They cause plant diseases: e.g., more than 900 viruses are
known to infect crop plants.
• They cause pet diseases such as rabies, Feline Leukemia
(FeLV), Feline Immunodeficiency (FIV), Canine Distemper.
• Genetic engineering: viruses can be used as a tool to move
genes from one organism to another.
HPV, An Emerging Plant Virus
• The high plains virus (HPV) was first found in 1993
infecting corn and winter wheat of the central and western
USA.
• By 1995, HPV was found to be widespread and cause
severe symptoms or death of maize, wheat, barley, and
several species of grasses.
• HPV is one of a family of plant viruses that cause wheat
spot mosaic, fig mosaic, thistle mosaic, rose rosette, and
redbud yellow ringspot diseases
• Aceria tosichella mite that transfers virus among plants.
• Corn HPV resistance genes have already been mapped and
may reduce mite feeding or the spread of the virus from the
point of infection.
Seal Plague Virus
Measles
Porpoise morbillivirus
Dolphin morbillivirus
Canine distemper
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Seal Plague Virus (PDV)
Harbor seal, Phoca vitulina
1988 Europe: population reduced
to 4,000 animals by 1989.
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2002 Europe: death toll 22,00030,000 animals out of a total
harbor seal population of 88,000.
Viruses Replicate in Two Ways
• Lytic Cycle: invades a host cell, takes over the
host’s DNA replication machinery, makes
more viruses. Virions then lyse host cell to
escape and infect other host cells.
• Lysogenic Cycle: invades host cell,
incorporates into host cell DNA, replicates
with host cell DNA and is transmitted to
descendant host cells like a host gene.
Types of Human Viral Diseases
• “Hit and Run”: produce acute disease in the individual and a
self-limiting epidemic in the human population, conferring
immunity on infected surviving individuals. Examples:
Influenza and smallpox.
• “Recurrent Disease”: persists in latent form after initial
infection and recurs during the life of the infected individual.
Examples: Chicken pox (shingles later in life) and herpes.
• “Endogenous Latency“: inserts into human germ cell lines
and is transmitted from host parent to host offspring like genes
for millions of generations. Examples: Human endogenous
retroviruses (HERTs).
Endogenous Retroviruses
• Endogenous retroviruses (ERVs) have invaded the germ-line
cells of every species of vertebrate and are transmitted, like
genes, as part of normal host reproduction.
• 8% of the human genome consists of HERVs.
• Host genomes are continually evolving new regulatory
mechanisms to silence the mutagenic effects on host genes
associated with the replication of HERVs. This results in a
reciprocal selective pressure on the HERVs to evolve to escape
the host controls.
HERV genes are in here,
~ 8,000 base pairs
5’ LTR
3’ LTR
Long Terminal Repeats (LTRs) are each ~1,000 base pairs
Evolution of LTRs of a Retrovirus Within a Single Species
At the time of insertion into the host germ-line cells,
the 5’ LTR and the 3’LTR are identical in gene sequence
Host
DNA
5’ LTR
Over time,
Mutations
Accumulate
3’ LTR
5’ LTR ≠ 3’ LTR
More time, Means More Mutations, which
Means
A Greater Difference Between 5’ and 3’
LTRs
5’ LTR ≠ ≠ ≠ 3’ LTR
Evolution of LTRs of an Endogenous Retrovirus Between Two Species
At the time of speciation from a common ancestor,
the 5’ LTR’s are identical in gene sequence and so are the 3’LTRs
Ancestor Species
Daughter Species 1
Mutations
Mutations
Daughter Species 2
Mutations
Mutations
5’ LTR of Species 1 ≠ ≠ ≠ 5’ LTR of Species 2
3’ LTR of Species 1 ≠ ≠ ≠ 3’ LTR of Species 2
Phylogeny of Primate Endogenous
Retroviruses
Gorilla
Human
5’ LTRs
Chimpanzee
Bonobo
Present
Past
Gorilla
Human
Chimpanzee
Bonobo
3’ LTRs
Human Immunodeficiency Virus (HIV), the
cause of AIDS
• HIV is a retrovirus (see Figure 26.5 in your text).
• HIV is called a lenti virus, owing to the long time it
takes to go from initial infection to disease.
• It is transmitted from infected to uninfected persons by
blood or semen.
• There are two genetically different kinds of HIV
circulating in the human population, HIV-1 and HIV-2
• Hypothesis: Humans acquired HIV by butchering and
eating from other primates.
Testing the Hypothesis that Humans
acquired HIV from other primates
1. Obtain SIV gene sequences from a variety of
primate species. Simian Immunodeficiency Virus =
SIV
2. Compare SIV gene sequences to HIV-1 and HIV-2
gene sequences.
3. The most similar DNA sequences share a more
recent common ancestor.
4. The most recent common SIV ancestor is the source
of HIV: HIV-1 Has a different origin than HIV-2.
Clade of Immunodeficiency Viruses
using SIV genes
African Green
Monkey
Sike’s
Monkey
Sooty
Mangabey
Mandrill
HIV-2
HIV-1
Chimpanzee
Support for the Hypothesis that Humans acquired
HIV by butchering and eating from other primates.
Refinement of the Hypothesis of the Origin of
HIV-1
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Which population of Chimpanzees did HIV-1 come from?
There are two chimpanzee subspecies in Africa: (1) Pan troglodytes troglodytes in
central Africa; and, (2) P. t. schweinfurthii in eastern Africa.
SIVcpz-1 is genetically very divergent from SIVcpz-2, consistent with the subspecies designation and the geographic distance between the subspecies.
Genetic and Bio-geographical Evidence for Sub-Specific origin of HIV-1
• All HIV-1 strains are closely related to SIVcpz-1. = Genetic Evidence.
• The natural range of P. t. troglodytes coincides uniquely with areas where the
Human population of Africa harbors HIV-1. = Geographic Evidence.
Conclusion: These two patterns indicate that P. t. troglodytes is the primary zoonotic
reservoir for HIV-1.
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Additional genetic evidence (not shown) suggests that there have been at least three
independent introductions of SIVcpz-1 into the human population!
Further testing of the Hypothesis
• Genetic evidence supports the Hypothesis that HIV is
a zoonotic infection, that is, our species has acquired
HIV at least twice from another species. Once from
the Chimpanzee and once from the Sooty Mangabey.
• From the view-point of the virus, infecting our
species is a host range expansion.
• Additional Hypothesis: If Humans acquired HIV by
eating ‘bush meat,’ then we should also carry other
blood-borne viruses from these same primates.
Simian foamy viruses (SFVs)
• Simian foamy viruses (SFVs) are ubiquitous,
non-pathogenic, non-endogenous retroviruses
that infect all primate species.
• Vertically transmitted from mother to
offspring, contagiously but not in the germline.
• They have co-speciated with Old World
Primates for over 30 million years: Every Old
World Primate Has its OWN UNIQUE SFV.
Genetic Evidence of Mother-Offspring Contagious Transmission of SFV
TREE or Clade from Primate
Maternally Transmitted
Mitochondrial DNA
TREE or Clade from SFV
Gene Sequence
No Human FV
• All foamy virus infections identified in humans are of
zoonotic origin and all have occurred in persons exposed to
non-human primates, like zoo keepers.
• Although humans share a common evolution with non-human
primates and are susceptible to SFV infection, humans are not
endemically infected with a species-specific FV like other
primates.
• Hypothesis: HFV became extinct in humans because of
reduced transmissibility from mother to offspring.
• Hypothesis: HFV exists endemically in some human
populations but they have not yet been tested.