Lecture 38 Flashcards
(23 cards)
What kind of interaction are virus-host interactions?
- 2 way interaction, often obvi started by virus that infects host
Virus-host interactions can be at different levels, what are the levels?
- Molecular level: how viral factors engage and use host cell factors and machinery to replicate, all viruses must enter cell and interact with receptors and use RNA/DNA polymerase also interact with sensors in cell as part of innate immunity
- cellular level: use resources => nutrients, nts, aa and everything from cell to synthesize viral genome nucleic acids and viral proteins
- organism level: responses from host aka immune response / IFN / Ab to target viral proteins, virus particle and virus infected cells to eliminate virus infection
- Population level: viral spread in populations and who is more vulnerable/resistant
What is cross-species transmission? Give examples of viruses
- From animals to humans and there could be an intermediate host, but viruses could spill back to animal like humans/mosquitos back and fort and SARS-CoV-2 to put pets, which poses a challenge since we cannot eradicate because in animals sets up server and can spill back into humans, some can never though like HIV cannot infect monkeys
- Influenza virus comes from birds
- HIV comes from non-human primates
- YFV comes from aides
Give examples of viruses that only infect humans
HepB, Small pox and polio
Describe the complex transmission of influenza
Comes from wild birds, natural reservoirs, infected at gut cuz that’s where the receptors are and this causes diarrhea. Then infect bats unidirectionally as well as domestic ducks and cats. Ducks can then 2 way infect poultry and one way horses and pigs. Cats can one way infect us and can one way get infected by poultry. Pig can 2 way infect us. Poultry is just one way, because changes had to be made to go from chicken to human and necessary changes cannot be made to reinfect chicken. Pigs can be mixing vessels as they can get infected by ducks and humans and since influenza is segmented, produces assorted virus.
Transmission of yellow fever virus
In urban, goes from mosquito to human to mosquito to human, not often human to human, in the wild can involve minkes and other non-human primates in the mix.
About the origins of AIDS viruses
- 36 mil have died from HIV and 38 mil continue to live with it
- Sooty mangabey gets infected by SIVsmm that can also infect macaques and in humans is HIV-2 which is limited to central Africa mostly although can be found elsewhere due to migration but prevalence fairly low
- Macaques can infect chimpanzees who then infect us and this is HIV-1 in humans and M type responsible for AIDS pandemic, chimpanzee very similar to us => replicates very well in our cells and causes a lot of damage, chimpanzees can also infect gorillas who spill back to us HIV-1 but type P and O and cases are quite limited
- Many monkeys have and coexist with SIV without treatment/antiretrovirals due to evolution bus those susceptible dies and the resistant ones survived #naturalselection, about 1/2 of monkeys have SIV though may not cause disease in them
First case of reported AIDS?
April 24, 1980, San Francisco resident ken horne is reported to CDC with Kaposi’s sarcoma very rare an painful skin cancer, he was also suffering from cryptococcus (lung infection very common in HIV patient) then HIV-1 was first isolated in 1983 but only sequenced in 1985, two groups isolated it but the French group got the Nobel prize, Gallo isolated HTLV, drama because USA and France fighting over who gets the patent
Cloning and sequencing of HIV-2
1986
- Morphologically similar, but antigenically distinct from HIV-1 so sera from HIV1 does not recognize HIV2 and vice versa, cause AIDS in patient in west Africa
- SARS-CoV-2 only two weeks to isolate, identify and sequence
What were the implication of sequencing SIVmac in 1987?
- Also caused AIDS in macaque, appeared genetically close to HIV 2 AIDS agent in West Africa, so speculation that HIV may come from monkeys
What were the implication of sequencing SIVsm in 1989?
- SIV only in monkeys in Africa => clues for where HIV may come from
- relation between SIVsm and SIVmac and HIV-2 because of similarity and determined order too (SIVsm => SIVmac and HIV-2)
What were the implication of sequencing SIVmac in 1990?
- Almost the same as HIV-1, probs infected humans and became HIV-1, mega clue
Phylogenetic tree of lentiviruses?
- Based on the pol gene, SIV chimpanzee and HIV-1 clustered together = closely related and HIV-2 clustered with SIVmac and SIVsm
A block in the road in the determination of HIV origins…
Analyses of 2000 captive-born or wild caught monkeys living in captivity, less than a dozen were SIVcpz positive o doubts about whether chimpanzees were true reservoir, so investigation instead of WILD apes/chimpanzees
What were the results of molecular epidemiology study of wild chimpanzee population in central Africa?
- Dif communities, do not mix due to different reasons
- Field studies of fecal and urine samples and looked for Ab positive specimens and did RNA extraction and RT-PCR and sequencing which meant that chimps were probably positive as well
- determined that prevalence was quite high, about half of each region was SIV positive, a little less in gorilla populations though
- Study gave really conclusive answers for whether chimpanzee SIV caused HIV-1 in humans and could allow for phylogenetic Tre construction
In the field study, how to know if fecal/urine sample from chimpanzee and not another animal?
- Had the sequence for mitochondrial DNA of chimpanzee to make sure
What new information was found d upon building the phylogenetic tree following the field study?
- Two tribes of monkeys, the troglodytes and schweinfurthii, both infected with SIV types but only troglodyte SIV was related to HIV-1
What are the four groups of HIV?
- M: cause of HIV pandemic, infected over 40 million people, now probably over 70 million
- N: less than 20 infections in Cameroon
- O: restricted to west central Africa, 100 000 infections
- P: 2 cases as of 2015
If we extend the lentivirus phylogenetic tree, what do we find?
- Many different species affected by lentiviruses
- rabbits even have an endogenous lentivirus which simply means that rabbits were infected so long ago that the lentivirus is now part of its genome
How do SIVs cross the species barrier and adapt to new hosts?
- Lesson learned from countering tetherin which holds virus particles to surfaces of producer cell => cannot be release and infect new cells
- HIV-1 no longer infects monkeys => cannot use them as animal model but tool can modify HIV-1 to infect monkeys and cause AIDS-like syndrome,
- Vpu and New both downregualte tetherin in SIVs related to HIV-1, then apes just new, but humans must use Vpu because nef cannot recognize tetherin in humans, sometimes when two species are closely related but two proteins are quite different it is because of positive selection to fight off pathogens
- Env protein down regulates tetherin in HIV-2 but before it was nef in monkeys but again Dif tetherin sequence had to evolve to use Env
- Example of the kinds of barrier and ways to overcome to cross species
About the evolutionary conflicts between viruses and hosts
- Arms race between host restriction factors and viral antagonists
- viral restriction factors inhibit viral infection and determine host tropism, who SIV cannot infect humans and HIV cannot infect monkeys
- Viral restriction factors undergo positive selection though mutations are random and not directional but certain pressure can exist and select when dN(non-synonymous change of aa)/dS(synonymous aa) is bigger than 1 means there is/was a pressure to change/select, if ratio is equal to 1, no selective pressure in either direction
Illustrate the arms race
viral antagonist attacks and degrades host restriction factor, so there is section for escape mutation and no successful viral antagonist but then selection of viral antagonists that regain interaction and degrade host restriction factor again but can select for a new escape mutant and this the co-evolution/arms race between virus/host
Who wins the arms race and how do hosts keep up?
- It depends, the virus has a smaller half-life BUT replicates a lot more faster
- Polymorphisms in the population, we are all different so gives viruses a run for their money, host heterozygosity => 2 copies of each gene could be different and offer an advantage, also gene duplication allows change of 2nd gene without consequence to host who has a functional copy and it may be some innovation that may set limitations on viruses (offers advantages in certain situations)
