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However, the biological basis of this interaction remains poorly understood and little is known about the impact of HIV on HCV replication at the cellular level. We analysed HCV RNA, based on single\u2010cell laser\u2010capture microdissection, in liver biopsies from monoinfected (n\u00a0=\u00a04) and HCV\/HIV\u2010coinfected (n\u00a0=\u00a05) participants. HCV RNA was assayed in 3200 hepatocytes with information of spatial position. We compared HCV RNA levels and clustering properties of infection between mono\u2010 and coinfected participants, and developed a mathematical model of infection. Although the median plasma HCV RNA level and the fraction of infected cells were comparable in monoinfected (7.0 log<jats:sub>10<\/jats:sub>IU\/mL and\u00a0~\u00a030%) and coinfected (7.3 log<jats:sub>10<\/jats:sub>IU\/mL and\u00a0~\u00a040%) participants, the median HCV RNA per infected hepatocyte in monoinfected (2.8IU) was significantly lower than in coinfected (8.2IU) participants (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.03). Clustering of infected cells was more prominent in monoinfected participants (91% of samples) than in coinfected participants (~48%), <jats:italic>p<\/jats:italic>\u00a0=\u00a0.0045, suggesting that spatial spread may be influenced by HIV coinfection. Interestingly, when clustering does occur, the size of clusters is similar in both types of infection. A mathematical model of infection suggested that HIV allows higher intracellular accumulation of HCV RNA by impeding the export of HCV RNA. Our observations show that HIV coinfection impacts intracellular accumulation of HCV RNA and the clustering of HCV\u2010infected cells, but to a less extent the fraction of HCV\u2010infected cells.<\/jats:p>","DOI":"10.1111\/jvh.13429","type":"journal-article","created":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T01:51:11Z","timestamp":1604109071000},"page":"334-344","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["HIV influences clustering and intracellular replication of hepatitis C virus"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1582-3379","authenticated-orcid":false,"given":"Ashish","family":"Goyal","sequence":"first","affiliation":[{"name":"Theoretical Biology and Biophysics Los Alamos National Laboratory Los Alamos NM USA"},{"name":"Vaccine and Infectious Disease Division Fred Hutchinson Cancer Research Center Seattle WA 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M.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Theoretical Biology and Biophysics Los Alamos National Laboratory Los Alamos NM USA"},{"name":"Laborat\u00f3rio de Biomatem\u00e1tica and Instituto de Sa\u00fade Ambiental Faculdade de Medicina da Universidade de Lisboa Lisbon 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