biostudies-literatureGianella SSwiss National Science FoundationNIAID NIH HHSNIMH NIH HHSNIGMS NIH HHS1703-9https://www.ebi.ac.uk/biostudies/studies/S-EPMC3472447biostudies-literatureUnknown84(11)The genital tract of individuals infected with human immunodeficiency virus type 1 (HIV-1) is an anatomic compartment that supports local HIV-1 and cytomegalovirus (CMV) replication. This study investigated the association of seminal CMV replication with changes in HIV-1 clonal expansion, evolution and phylogenetic compartmentalization between blood and semen. Fourteen paired blood and semen samples were analyzed from four untreated subjects. Clonal sequences (n?=?607) were generated from extracted HIV-1 RNA (env C2-V3 region), and HIV-1 and CMV levels were measured in the seminal plasma by real-time PCR. Sequence alignments were evaluated for: (i) viral compartmentalization between semen and blood samples using Slatkin-Maddison and F(ST) methods, (ii) different nucleotide substitution rates in semen and blood, and (iii) association between proportions of clonal HIV-1 sequences in each compartment and seminal CMV levels. Half of the semen samples had detectable CMV DNA, with at least one CMV positive sample for each patient. Seminal CMV DNA levels correlated positively with seminal HIV-1 RNA levels (Spearman P?=?0.05). A trend towards an association between compartmentalization of HIV-1 sequences sampled from blood and semen and presence of seminal CMV was observed (Cochran Q test P?=?0.12). Evolutionary rates between semen and blood HIV-1 populations did not differ significantly, and there was no significant association between seminal CMV DNA levels and the frequency of non-unique clonal HIV-1 sequences in the semen. In conclusion, the effects of CMV replication on HIV-1 viral and immunologic dynamics within the male genital tract are not significant enough to perturb evolution or disrupt compartmentalization in the genital tract.Journal of medical virologyImpact of seminal cytomegalovirus replication on HIV-1 dynamics between blood and semen.PMC3472447P30 MH062512P01 AI074621AI043638AI36214R24 AI106039AI69432AI077304U01 AI043638R01 GM093939R21 AI080353P30 AI036214125533R21 AI047745R56 AI047745GM093939R01 AI047745MH083552MH62512R21 AI077304AI080353AI74621R01 MH083552U01 AI069432K23 AI093163UM1 AI069432AI047745Little SJGianella SVargas MVMehta SRKosakovsky Pond SLSmith DMStrain MCYoung JARichman DDfalseImpact of seminal cytomegalovirus replication on HIV-1 dynamics between blood and semen.The genital tract of individuals infected with human immunodeficiency virus type 1 (HIV-1) is an anatomic compartment that supports local HIV-1 and cytomegalovirus (CMV) replication. This study investigated the association of seminal CMV replication with changes in HIV-1 clonal expansion, evolution and phylogenetic compartmentalization between blood and semen. Fourteen paired blood and semen samples were analyzed from four untreated subjects. Clonal sequences (n?=?607) were generated from extracted HIV-1 RNA (env C2-V3 region), and HIV-1 and CMV levels were measured in the seminal plasma by real-time PCR. Sequence alignments were evaluated for: (i) viral compartmentalization between semen and blood samples using Slatkin-Maddison and F(ST) methods, (ii) different nucleotide substitution rates in semen and blood, and (iii) association between proportions of clonal HIV-1 sequences in each compartment and seminal CMV levels. Half of the semen samples had detectable CMV DNA, with at least one CMV positive sample for each patient. Seminal CMV DNA levels correlated positively with seminal HIV-1 RNA levels (Spearman P?=?0.05). A trend towards an association between compartmentalization of HIV-1 sequences sampled from blood and semen and presence of seminal CMV was observed (Cochran Q test P?=?0.12). Evolutionary rates between semen and blood HIV-1 populations did not differ significantly, and there was no significant association between seminal CMV DNA levels and the frequency of non-unique clonal HIV-1 sequences in the semen. In conclusion, the effects of CMV replication on HIV-1 viral and immunologic dynamics within the male genital tract are not significant enough to perturb evolution or disrupt compartmentalization in the genital tract.2012-01-01T00:00:00Z2012 Nov2021-02-20T09:01:23Z2019-03-27T00:59:08ZS-EPMC34724472299707210.1002/jmv.23398