20 Virus: HIV and emerging viruses

Question 1

short emerging virus defintion

Answer 1

Causative agent of a new or previously unrecognized virus infection

Question 2

5 stages of emerging viruses and examples

Answer 2

1
virus only in animals

2
virus can infect humans, but only zoonotic e.g. Rabies

3
Virus can lead to primary infections and in some cases human to human transmission is possible e.g. Ebola

4
longer outbreaks with human to human transmission possible e.g. Dengue

5
only human to human transmission e.g. HIV-1

Question 3

Terminology
enzootic
Epizootic
Panzootic

Answer 3

enzootic
endemic
Epizootic
epidemic
Panzootic
pandemic

Question 4

Factors that drive emergence of viruses (6)

Answer 4

Enviromental factors
changing enviroments
Yellow fever (climate change)

Economic, social factors
Megacities, globalization
Small pox
Poliovirus

Microbe and Viruses
opportunistic infections

Human and Animal
Pets, Livestock, Xenotransplants
Zoonosis, Ebola, Influenza, Corona

Ecological factors

Genetic and biological factors
evolution, Avian influenza

Question 5

4 virus host interactions and examples

Answer 5

Stable
virus/host survive and multiply, sometimes infection of many species

e.g. HSV, Measles

Evolving
instability and unpredictability
Infection can be asymptomatic or lead to death, virus can aquire new properties that increase spread

e.g. Introduction of Smallpox into Natives America colonization

Dead end
cross species infection, often host killed without spread or transmission isnt even possible

e.g. Rabies, Arboviruses (chicken, but not humans), Ebola, Dengue

Resistent
Host is resistent because it does not have the right receptor for viral spread

Question 6

Name 2 evolutionary distinct groups of retroviruses

Answer 6

Deltaretrovirus
HTLV 1-4

Lentivirus
HIV-1, HIV-2, SIV

Question 7

Origin of HIV and which strain is more relevant?

Answer 7

Origin is non human primates

HIV-1 is more virulent, transmission easier

Question 8

HIV genome
how many genes?
Which genes are common to all retroviruses?
Infectious cycle

Answer 8

how many genes?
9 genes

Which genes are common to all retroviruses?
gag (group specific antigen)
Membrane targeting, budding, virion core structure, virion packaging

pol (polymerase)
Integrase, RT, Protease

env (envelope)
surface glycoprotein and transmembrane glycoprotein

Infectious cycle

HIV Virion with 2 copies of +ssRNA and packed Integrase, RT and Protease

Binding to CD4 receptor
Fusion
DNA Synthesis with RT
DNA Splicing / Integration via Integrase
Transcription
Translation
Virion assembly
Budding
Maturation (Protease)

Question 9

HAART therapy
defintion
which targets (5)

Answer 9

using multiple drugs: 3-4 drugs using at least 2 different targets:

Entry inhibitor
Integrase inhibitor
Protease inhibitor
RT inhibitor
Maturation inhibitor

Question 10

How did the Berlin patient overcome HIV infection?

Answer 10

He received a hematopoetic stem cell transplant from a donor with delta 32 mutation on CCR5 receptor

HIV cannot enter without coreceptor so if you are homzygous for this mutation you wont get HIV infection

Question 11

Cell tropism

Answer 11

different strains of HIV
R5: CCR5 macrophages
X4: Cxcr4 t cells

but does not alone explan tropism because R5 not always productive infection using CCR5

Question 12

Hallmarks of AIDS

Answer 12

reduced T cell counts
infected / uninfected T cells die
less than 200 CD4+ cells/ml

Opportunistic infections
Toxoplasma,
Mycobacteria
Candida, PcP
HSV, CMV

Immune activation
HIV replicates better in activated t cells

Malignancies
40% through high levels of cytokines (ROS, …) e.g. Karposi sarcoma by HHV-8

Neurological symptoms
AIDS dementia complex

Question 13

HIV transmission

Answer 13

sexual
vertical (rare, mostly only replication in placenta)
injection
blood transfusion
occupational exposure

Question 14

Variable course of infection

What is an elite controller?

Answer 14

typical progressor
AIDS after some years

rapid progressor
AIDS after some months

Nonprogressor
latency

Elite controller
person that maintains a normal CD4 count and undetectable virus load for more than 10 years without HAART

associated with favorable HLA types and T cell responses, but not with attenuated viruses

Question 15

HIV-1 Host restriction factors

Answer 15

APOBEC3
if vif gene absent, it can edit cytidines, resulting in Guanosin to adenosin mutations to lose gentic integrity

TRIM5alpha
barrier for cross species transmission of primate lentiviruses

Tetherin
trapping of virion at surface, but vpu gene works as antagonist

Question 16

Establishment of HIV infection

Answer 16

Active viral replication maintained
10^9 virions produced and destroyed / day, halftime is only couple of hours

Reservoir exist outside of blood
e.g. Nervous system or Genital tract

Question 17

Figures
newly infected
people living with HIV
deaths

Answer 17

newly infected
1.5M decreasing

People living with HIV
40M, 15% did not not ther status

Deaths
650k

Question 18

Origin of HIV

Are there still groups of HIV with no human to human transmission?

Answer 18

HIV-1 and HIV-2
Seperate colonization events of SIV in humans, multiple transmission events, but only one lead to human to human transmission

SIV
pathogen in many monkey species, same transmission routes

How
Cross species infection:

Chimpanzee Human
HIV-1 M and N (and O)

chimpanzee - western gorilla- human
HIV-1 P (and O)

Mangabey Human
HIV-2 A-H

Are there still groups of HIV with no human to human transmission?
each group different transmission event, group P and N only few cross species transmission events

How did they infect humans?
Bushmeat hunting, membrane exposure to infected chimpanzee blood

Question 19

Founder effect

Answer 19

First transmission leads to outbreak, the first strain of a region then probaby stay the major strain

Question 20

Prophylaxis

Answer 20

Promising studies for broadly neutralizing antibodies