HIV & AIDS I

Retroviridae

What family is HIV in?

lentivirus

What is the HIV genus?

humans and apes

What species have his?

Single-stranded, positive-sense RNA genome

Hiv genome structure

Describes the slow disease progression of the founding member of the genus, visna virus of sheep

What does the retro, for retroviridae mean?

sexual contact, blood, breastfeeding

How are retroviruses transmitted?

Mature and Immature

What are the two versions of a retrovirus?

AIDS

HIV causes

HIV

Human Immunodeficiency Virus

Acquired Immunodeficiency Syndrome

AIDS

CD4+T cell depletion

AIDS results from

it causes severe immunosuppression and an increase in susceptibility to viruses

What does CD4+T cell depletion do?

global public health issue

The HIV Pandemic remains a Major

40 million

How many people currently live with HIV?

tens of millions

______________ of people have died from AIDS

Antiretroviral therapy

What is used to treat HIV?

drug

Antiretroviral therapy is a ____ based therapy

no

Is there a vaccine for HIV?

cure

HIV and AIDS has no scalable ____

Women

In Africa, do mean or women get HIV more?

0.7%

How many adults have HIV?

1.3 million

How many new HIV infections were there in 2024?

3.1%

How many people in Africa live with HIV?

occurring

new HIV infections are still

teenage

In Africa many ______ girls become infected

zoonosis

HIV is a

HV-1 Clade M spread worldwide

What caused the HIV pandemic?

Historical records, Sequencing of virus isolates from people across time, Sequences from monkey/ape shit

How do we know about origins of the HIV pandemic?

HIV-1 & HIV-2

What are the 2 distinct lentiviruses humans have?

unique cross-species transmissions

Where do human lentiviruses come from?

Simian Immunodeficiency Viruses (SIVs)

What is closely related to HIV?

an endemic lentivirus (SIV)

Over 40 species of African monkeys have

people

Many examples of the disease jumping into

chimps and gorillas

What has often been the cause for the jump?

because we are closely related

Why is it easier for chimps and gorillas to transfer disease to people?

Group M

What is the major HIV-1 Group?

>50,000,000

How many cases of Group M are there?

12

How many subtypes of Group M exist?

8 (A-H)

How many clades are there in Group M?

C and B

What are the most common clades seen in Group M?

-2,000,000

How many cases of HIV-2 are there?

Group A

What group of HIV-2 is the most pandemic?

pathogenic

HIV-2 is less __________ than Hiv-1

sooty mangabeys

What is the origin of HIV-2?

blood-blood transfer during the butchering of bushmeat (for food
and income)

How did SIV jump into humans?

zoonotic event

HIV to chimp to human transition was a

animal reservoir (unlike rabies)

HIV causing the global pandemic is not repeatedly spread from an

1900s

HIV-1 origins dated to early

primates

Currently there are no lentiviruses in

June 1981

Morbidity Mortality Weekly Report Provided early indicators of HIV (people dying of hard to contract illness)

September 1982

AIDS gets defined as an illness in the US

December of 1982

case of AIDS after blood transfusion reported

1985

FDA bans gay men from donating blood

March 1983

CDC addresses transmission

January 1983

“Ward 86” Opens at UCSF as the first outpatient AIDS clinic in the country

AIDS activism

June 1983

May 1983

HIV is discovered as the virus that causes AIDS

Took Cultured t cells from lymph nodes of the infected and transcribed them to recognize the reverse transcriptase

How was it discovered that HIV causes AIDS?

January 1985

CDC comes forward saying HIV causes AIDS, First public mention of AIDS by Ronald Reagan

March 1987

ACT UP (AIDS Coalition to Unleash Power) Forms as grassroots political group working to end the AIDS pandemic, FDA approves first antiretroviral drug (Zidovudine = AZT)

1992

AIDS becomes #1 cause of death for US men aged 25-44

The virion surface is a lipid bilayer coated with envelope timers and these are supported by MA (matrix) proteins

Structure of the mature HIV-1 virus particle

lipid bilayer coated with Envelope timers and these are
supported by MA(matrix) proteins underneath

the virion layer

additional viral enzymes, accessory proteins, and host proteins and RNA

Internal space is occupied by

CA (capsid) lattice

Core is made up of

RNA genomes (single-stranded, plus sense) coated by NC (nucleocapsid) and reverse transcriptase

Core contains two

Gag, Pol, Env

Multiple viral proteins are made from the three key precursor proteins

Gag

processed to form Matrix protein, Capsid protein, Others

Pol

processed to form: Reverse transcriptase, Protease, Integrase

Env

processed to form: Surface subunit or SU, Transmembrane subunit or TM

conical core structure (genome inside)

HIV virions in their “mature” form have a characteristic

nucleus through the nuclear pore

Shape of this ‘core’ may help in entering the

First, the virus attaches to the CD4 receptor on T cells (binding mediated by Env), Env mediates membrane fusion, The viral capsid and RNA genome are delivered into the cell

HIV Viral Lifecycle Part I: Entry

CD4+ T cells, Macrophages, Dendritic cells

HIV infects

CD4 and CCR5/CXCR4 receptor usage

HIV preferentially infects immune cells due to

CD4

Receptor is

helper T cells (CD4 cells), macrophages and dendritic cells

Where is CD4 found?

CCR5

co-receptor

Expressed on T cells and (especially memory cells) and macrophages

CCR5 is

CXCR4

more widely used co-receptor

not sufficient to mediate viral entry

CD4 on a host cell is necessary but

permit viral entry

A second receptor called the co-receptor is required to

chemokine receptors

CCR5 and CXCR4 are called

to detect the chemical signals (called chemokines) that tell immune cells where to travel in the body

What is the normal function of CCR5 and CXCR4?

viral and cell membranes

HIV envelope (surface glycoprotein) undergoes complicated changes in shape to mediate fusion of

HIV envelope

Both receptor and co-receptor bind to

First, Env on the virus attaches to the CD4 receptor on T cells, then, Env mediates membrane fusion, and viral capsid and RNA genome are delivered, then the RNA genome is reverse
transcribed into DNA

HIV Viral Lifecycle Part II: Reverse Transcription and Integration

RNA genomes

Retroviruses have small

Reverse Transcriptase

All Retroviruses use an enzyme called

makes a DNA copy of their RNA genome

What does Reverse Transcriptase do?

the host DNA genome (through a process called integration)

The DNA copy of the viral genome inserts itself into

cells they infect

Retroviruses become a permanent part of the

Central Dogma

Retroviruses: In Conflict with The