- Vif gene is one of the important regulatory gene in lifecycle of HIV virus. It was observed that HIV virus with mutated Vif gene fails to culture of normal T- helper cells. The main reason is
(1) Vif gene helps in reverse transcription process
(2) Vif gene helps in transport of HIV genome to nucleus
(3) Vif gene helps in insertion of viral genome into host genome
(4) Vif product targets the enzyme responsible for hypermutaion to ubiquitination and cellular
degradationThe correct answer is (4) Vif product targets the enzyme responsible for hypermutation to ubiquitination and cellular degradation.
Mechanism in brief
Normal CD4⁺ T helper cells express APOBEC3G, a cytidine deaminase that incorporates into budding HIV virions and, during reverse transcription in the next host cell, deaminates cytidines in minus-strand viral DNA, causing G→A hypermutations that render the virus non‑infectious.
HIV’s Vif protein counteracts this by forming a complex with APOBEC3G and a Cullin5–ElonginB/C E3 ubiquitin ligase, leading to ubiquitination and proteasomal degradation of APOBEC3G.
If Vif is mutated or absent, APOBEC3G is not degraded, enters virions, and induces lethal hypermutation, so the virus fails to grow in normal T helper cells.
Option-wise explanation
(1) “Vif gene helps in reverse transcription process.” – Incorrect
Reverse transcription is carried out by reverse transcriptase; Vif is not required for the enzymatic synthesis of viral DNA, but rather for protecting the viral genome from APOBEC3G during this phase.
(2) “Vif gene helps in transport of HIV genome to nucleus.” – Incorrect
Nuclear import of the pre‑integration complex is mainly mediated by integrase, matrix, and Vpr, not Vif. Vif’s primary known role is in counteracting host restriction factors, not nuclear transport.
(3) “Vif gene helps in insertion of viral genome into host genome.” – Incorrect
Integration into the host genome is catalyzed by integrase. Vif does not function as an integrase nor is it essential for the integration reaction itself.
(4) “Vif product targets the enzyme responsible for hypermutation to ubiquitination and cellular degradation.” – Correct
The “enzyme responsible for hypermutation” is APOBEC3G (and related APOBEC3s), which deaminate cytidines in viral cDNA causing lethal mutations.
Vif binds APOBEC3G and recruits a Cullin5-based E3 ubiquitin ligase, tagging APOBEC3G for ubiquitination and proteasomal degradation, thereby preventing its incorporation into new virions and avoiding hypermutation.Thus, HIV with a mutated Vif cannot degrade APOBEC3G, leading to APOBEC3G‑mediated hypermutation and loss of viral infectivity in normal T helper cells—why such virus “fails to culture” these cells.
In summary, Vif is essential because it protects HIV from APOBEC3G-induced hypermutation by targeting APOBEC3G for ubiquitin‑mediated degradation, as stated in option (4).
