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Transcript of HIV
by "budding" Another
approach Type I Interferon Is a Powerful Inhibitor of in Vivo HIV-1 Infection and Preserves Human CD41
T Cells from Virus-Induced Depletion in SCID Mice Transplanted with Human Cells Caterina Lapenta, Stefano M. Santini, Enrico Proietti, Paola Rizza, Mariantonia Logozzi, Massimo Spada,
Stefania Parlato, Stefano Fais, Paula M. Pitha and Filippo Belardelli Type 1 Interferon (IFN) Cytokine
Warns nearby cells A blessing or a curse? Inhibitory effects in vitro
Can inhibit the proliferation of T-cells
HIV induces the production of IFN Study in vivo SCID (Severe Combined ImmunoDeficiency) mice transplanted with human cells INF AZT control Results Powerful inhibitor of HIV-1
More effective than AZT
Stimulates anti-HIV-1 response Homotypic bivalent binding is not possible for HIV These guys change - QUICKLY B-cells: Engineers of immune response
Produces Antibodies Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation T-cells Troops of immune response
Coordinate and carry out counter offensive Hugo Mouquet, Johannes F. Scheid, Markus J. Zoller, Michelle Krogsgaard, Rene G. Ott, Shetha Shukair HIV-RNA is prone to mutation! Heteroligation - Indicates that one antibody is binding two different antigens Primary response peaks c:a 20 days after infection Polyreactive antibodies bind to secondary structure Low affinity binding Spike Tramnsmembrane protein (CXCR4 or CKR5) HIV recognices the CD4 receptor CD4 Anatomy of the retrovirus HIV Two copies of single-stranded RNA 3 Enzymes
integrase Protective capsid lipoprotein layer derived from host cells membrane Any studies on this? RNA is transcribed into DNA with reverse-transcriptase
Double helix DNA is formed Viral DNA is integrated into
host chromosome with integrase
Necessary proteins are made when RNA is
translated "the existence of heteroligation and its contribution to anti-HIV antibody affinity suggests that mimicking the low-density viral antigens encountered during natural infection should be considered as a means to enhance anti-HIV immunization." Budding: Virion leaves the cell encoating itself with part of the host's membrane
Protease matures the virion after budding has occured
Average life-span of host cell
after infection: 2.2 days HIV "Antibodies specific for conserved regions of the HIV spike protein have the ability to neutralize the virus and prevent infection in nonhuman primates" Parts of gp-spikes are highly conserved glycoprotein spike Two transmembrane proteins Low density of surface spikes B-cells tend to favour homotypic antibodies Antibodies targeting conserved regions are rare polyreactive - binds to many different epitopes Implications for vaccine design promote polyreactivity and heteroligation Immune response Carried out by two types of cells Up to 105 times/day HIV destroys the immune system by killing it and crippling it Infection of T-Helpers Helper cells secrete signal proteins to activate killer cells
HIV may inhibit this secretion