HUMAN IMMUNODEFICIENCY

VIRUS

Fort Salvador
 • Enveloped, helical, positive-sense diploid ssRNA virus – Retroviridae
• HIV 1 and HIV 2; serotype M responsible for global spread
• Infects CD4+ helper T cells, macrophages, and monocytes
• Three major genes – pol, gag, env
• gag – internal core genes; p24 (important in HIV testing)
• pol – reverse transcriptase, integrase, protease
GENERAL • env – gp160 cleaved into gp120 and gp41 (surface glycoproteins)
CHARACTERISTIC • Antigenic differences in gp120 used to divide in clades
S
 GENERAL CHARACTERISTICS

• Capsid proteins
• Reverse transcriptase – no editing function; RNA-dependent DNA polymerase
• Integrase
• Protease
• Regulatory protein – Tat (activates transcription) and Nef (repress MHCI)
• Accessory protein – Vif (inhibits APOBEC3G which inactivates viral genes)
 GENERAL
CHARACTERISTICS

• gp120 – interacts with CD4 receptor;

mutates rapidly
• gp41 – mediates fusion
• p24 – induces non-neutralizing antibodies;
used for testing
 GENERAL CHARACTERISTICS

• Humans are the only infected species

• May have been descended from chimpanzee viruses
• Simian immunodeficiency virus
• HIV 2 is HIV1’s less transmissible brother
• Localized to West Africa
 REPLICATIVE CYCLE

• Binding to gp120 and another chemokine receptor (depending on the cell type)
• gp41 mediates fusion
• CXCR4 – for T-cell tropic strains
• CCR5 – macrophage-tropic strains
• Homozygotes for these receptors are immune
• Reverse transcriptase transcribes RNA into DNA in the cytoplasm
• Integrase integrates (provirus)
 REPLICATIVE CYCLE

• Transcribed by host RNA polymerase; guided by cyclin T1 and Tat

• Gag and Pol cleaved by viral protease
• Env cleaved by cell protease
 TRANSMISSION

• Primarily by sexual contact

• Transplacentally, through the birth canal, breast milk
• Can be due to infected cells or free HIV
• Infectious dose is high
• People with STIs have a higher chance of infection
• Uncircumcized males
 PATHOGENESIS

• Infects CD4+ cells – depleted CMI

• First infects dendritic cells then spreads to local CD4 + cells
• Found in the blood after 4-11 days
• Infects TH17 cells (mucosal immunity)
• Infects brain monocytes
• Cells recruited into a syncytium and die; or be attacked by CD8 + T cells
• Certain T cells (in lymph nodes) may remain immortal while producing virions
• Can establish a true latent state
 PATHOGENESIS

• Activation of B cells – autoimmune diseases (thrombocytopenia, etc.)

• CD8+ T cells fail – no stimulation
• No MHC1
• No new clone formation
• Evasion of immune system
• Integration of viral DNA
• Env mutation
• Low MHCI presentation
 SUBSETS OF INFECTION

• Normally infected
• Elite controllers (no detectable HIV in blood)
• Nef gene mutants (no decrease in MHC1 expression), α-Defensin
overproducers (interfere with CXCR4 binding)
CLINICAL
FINDINGS
 CLINICAL FINDINGS

• Acute stage (2-4 weeks after infection)

• Mononucleosis-like (fever, sore throat, generalized
lymphadenopathy)
• Maculopapular rash on the body sparing the palms
and soles
• High level viremia (very infectious), leukopenia BUT
high CD8+ cells
• Antibodies rise 10-14 days after infection (false-
negatives)
• Viral setpoint occurs – higher, more symptomatic
• Tested in an assay
• CD4+ counts also affect prognosis (below 200/μL)
 CLINICAL FINDINGS

• Clinical latent phase (measured in years)

• Viral lymph node cells keep producing, but remain sequestered
• AIDS-related complex (multiple fevers, lymphadenopathy, fatigue, weight loss)
• AIDS (CD4+ count below 200/μL)
• Opportunistic infections
 LABORATORY TESTING

• Combo testing – both p24 and antibodies

• Proceeds to distinguish between HIV1 and 2
• PCR to detect viral RNA
• Viral load and CD4+ cell count
 TREATMENT

• Multidrug treatment to prevent resistance

• Emtricitabine and tenofovir + efavirenz, raltegravir, rilpivirine, ritonavir, darunavir
• Nucleos/tide reverse transcriptase inhibitors – chain terminators
• Protease inhibitors
• Fusion inhibitors
• Integrase inhibitors
• Immune reconstitution inflammatory syndrome
• Prevented by post-exposure prophylaxis in susceptible populations and infected
mothers