RhoB is a component of the human cytomegalovirus assembly complex and is required for efficient viral production

<p>Human Cytomegalovirus (HCMV), an ubiquitous β-herpesvirus, is a significant pathogen that causes medically severe diseases in immunocompromised individuals and in congenitally infected neonates. RhoB belongs to the family of Rho GTPases, which regulates diverse cellular processes. Rho proteins are implicated in the entry and egress from the host cell of mainly α- and γ-herpesviruses, whereas β-herpesviruses are the least studied in this regard. Here, we studied the role of RhoB GTPase during HCMV lytic infection. Microscopy analysis, both in fixed and live infected cells showed that RhoB was translocated to the assembly complex/compartment (AC) of HCMV, a cytoplasmic zone in infected cells where many viral structural proteins are known to accumulate and assembly of new virions takes place. Furthermore, RhoB was localized at the AC even when the expression of the late HCMV AC proteins was inhibited. At the very late stages of infection, cellular projections were formed containing RhoB and HCMV virions, potentially contributing to the successful viral spread. Interestingly, the knockdown of RhoB in HCMV-infected cells resulted in a significant reduction of the virus titer and could also affect the accumulation of AC viral proteins at this subcellular compartment. RhoB knockdown also affected actin fibers' structure. Actin reorganization was observed at late stages of infection originating from the viral AC and surrounding the cellular projections, implying a potential interplay between RhoB and actin during HCMV assembly and egress. In conclusion, our results demonstrate for the first time that RhoB is a constituent of the viral AC and is required for HCMV productive infection.</p

Genotypic distribution for KIF1B gene polymorphisms when patient (Cases I+II+III+IV) group was compared to control group.

<p>Risk allele marked in <b>BOLD</b> letter.</p

Haplotypes of KIF1B gene variants when patient (Cases I+II+III+IV) group was compared to control group.

<p>♦This value is insignificant when Bonefforoni correction was applied.</p

SNP marker information for KIF1B gene for all subjects studied (patients and healthy controls).

<p>Chr. No.: Chromosome Number; SNPs: Single Nucleotide Polymorphisms; Position: Chromosomal Position; ObsHET: Observed Heterozygosity; PredHET: Predicted Heterozygosity; HWpval: Hardy-Weinberg P-value; MAF: Minor Allele Frequency.</p

Genotypic distribution for KIF1B gene polymorphisms when cases II+III+IV were compared to case I (inactive group).

<p>Risk allele marked in <b>BOLD</b> letter.</p

Haplotypes of KIF1B gene variants when Cases III+IV groups were compared to case II (active group).

<p>Haplotypes of KIF1B gene variants when Cases III+IV groups were compared to case II (active group).</p

Genotypic distribution for KIF1B gene polymorphisms when cases III+IV groups were compared to case II (active group).

<p>Risk allele marked in <b>BOLD</b> letter.</p