NOVEL APPROACHES IN

HIV_AIDS

By . . ,DR CH.PAVAN KUMARMBBS

NOVEL UDERSTANDING OF EPIDEMIOLOGY.

APPLICATIONS.

 

EPIDEMIOLOGY

HIV VIRUS

ENVIRONMENT

HOST

        AIDS

HOST

ENVIRONMENTAGENT

HIV VIRUS

V1/V2

env

mannose

cholesterol

CD 59

HIV VIRUS“env” is the most used target for the

production for vaccines.

In 2012, An anti-SIVSME543 vaccine

obligately including “env “protein antigens prevented SIV in rhesus monkeys.

HIV hides inside coat rich in mannose.

pradimicin A1.Freezes HIV's molecular

machinery for entering and infecting its host's healthy cells.

2.The virus responds by reducing the mannose in its coat thereby revealing itself to the immune system, which can then attack.

Contd..,

The antibody binding site, called the V1/V2 region, represents a suitable HIV vaccine target.

CD59 protien of human origin will be kept in capsid of HIV thereby escaping the immune mechanism.

Contd….,

HIV rotates and flattens, exposing more of the gp41 proteins in the middle during attachment.

Probably allowing the gp41 protein to get closer to the cell membrane so it can lock on.

Exposes an area of the virus that would be vulnerable to attack by the immune system.

Contd….,

HIV

CD4+ CELL

Vulnerable area

HIV

CD4+ CELL

ENVIRONMENT

The LENTIVIRAL VECTOR has only been tested in culture dishes and has resulted in the destruction of about 35 percent of existing HIV cells.

Breast milk antibodies. . ,Nearly half of the 350,000 new infant HIV

infections occurring annually are transmitted via breast milk .

(can it kept here or to be shifted to the host).

The human body can produce powerful antibodies that shield cells in the laboratory against infection by an array of HIV strains.

Antibody-dependent cell-mediated cytotoxicity is important.

Appearing only after a person has been infected with HIV for at least one year.

IL 7 seem to be important.

HOST

CD4+ T cells with the α4β7 receptor play an role in the sexual transmission of HIV.

Cofilin , a protein used to cut through a cell's outer layer, or cytoskeleton -- is involved in HIV infection.

LIM domain kinase, triggers a cell to move, like a propeller. This cell movement is essential for HIV infection.

Contd….,

A sugar-binding protein called galectin-9 traps PDI (protein disulfide isomerase)on T-cells.

PDI helps,Change the shape of the surface

envelope protein of the virus .Enabling the virus to interact

optimally with receptors as the CD4 molecule.

Contd….,

• In certain monkeys TRIM5,cellular protein,– Recognizes this lattice structure,– Specifically attaches itself to it,

Stimulates the protein to produce signal molecules known as polyubiquitin chains in the cell.

These chains immediately trigger an anti-viral reaction.

The "alerted" cell can then start eliminating cells infected with HIV by releasing messenger substances (cytokines).

Contd….,

Protein named SAMHD1 was able to prevent HIV_1 ,– is able to degrade deoxynucleotides(dNTP) ,

which are the building blocks required for replication of the virus.

Alarmins ,Ex: Interleukin 33.Create the foreign look and presented by

dentritc cells to t cells.IL-33 could be used to artificially increase the T

killer cell army, which was generated in response to vaccination.

Contd….,

Capsid protein, acting like a key, binds to Nup358, a protein on the nuclear pore complex gain access to nucleus.

Gene TLR7 allows the antibody generating B cells. To detect the presence of a retrovirus. Germinal centre reaction.

Contd….,

Human Endogenous RetroViruses (HERV’s),Are genetic fossils of retro viruses with HIV 

activates HERVs that lie inside HIV-infected cells in some individuals.

The activated HERVs produce proteins that attract immune system T cells to the HIV-infected cells.

HLA alleles [critical immune system components] that are associated with protection from HIV-1 disease progression.

Proteins produced by the HERV genes can act as target.

Contd….,

Elite suppressors (0.5 percent of all HIV-infected individuals)infected with the virus, (more effective killer T cells,) are naturally able to control infection in the absence of antiretroviral therapy, or HAART.

Levels of HIV integrated into immune cells are much lower.

Cells that contain the integrated form of HIV DNA and are metabolically less active.

Contd….,

A transdermal patch which releases more than 96 percent of the hiv medication over the course of seven days.

 

Economic advantage.With an estimated 15 million people living with HIV in developing countries and only 5.3 million people with access to treatment.

More..,

HVTN 505 is testing the safety and efficacy of a TWO-PART HIV VACCINE REGIMEN. – Prime the immune system. – Boost the immune response.

A major HIV vaccine RV144 trial trial in Thailand showed for the first time that a vaccine can generate modest protection against HIV infection in humans.

Gene Therapy, to insert genetically mutated viruses into living cells.

Contd….,