Viral infectivity factor
Encyclopedia
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
found in HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
and other retrovirus
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
es. Its role is to disrupt the antiviral activity of the human enzyme APOBEC
APOBEC
300px|thumb|upright|alt = Colored dice with checkered background|Example of a member of the APOBEC family, APOBEC-2. A cytidine deaminase from Homo Sapiens....
(See also APOBEC3G
APOBEC3G
APOBEC3G is a human enzyme encoded by the APOBEC3G gene that belongs to the APOBEC superfamily of proteins. This family of proteins has been suggested to play an important role in innate anti-viral immunity...
) by targeting it for ubiquitination and cellular degradation. APOBEC
APOBEC
300px|thumb|upright|alt = Colored dice with checkered background|Example of a member of the APOBEC family, APOBEC-2. A cytidine deaminase from Homo Sapiens....
is a cytidine deaminase enzyme that mutates viral nucleic acids.
Vif is a 23-kilodalton protein that is essential for viral replication. Vif inhibits the cellular protein, APOBEC3G
APOBEC3G
APOBEC3G is a human enzyme encoded by the APOBEC3G gene that belongs to the APOBEC superfamily of proteins. This family of proteins has been suggested to play an important role in innate anti-viral immunity...
, from entering the virion during budding from a host cell by targeting it for proteasomal degradation. Vif hijacks the cellular Cullin5 E3 ubiquitin ligase, which is composed of ElonginB, ElonginC, Cullin5, and Rbx2,(Crystal Structure of the HIV Vif BC-box in Complex with Human ElonginB and ElonginC is solved and shown here ) in order to target APOBEC3G for degradation. In the absence of Vif, APOBEC3G causes hypermutation of the viral genome, rendering it dead-on-arrival at the next host cell. APOBEC3G is thus a host defence to retroviral infection which HIV-1 has overcome by the acquisition of Vif. Targeting vif has been suggested as a strategy for future HIV drug therapies.