Title: HIV influences clustering and intracellular replication of hepatitis C virus

Abstract

We report HCV and HIV coinfection is common and HIV leads to increased HCV viraemia and accelerated disease progression. 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-cell laser-capture microdissection, in liver biopsies from monoinfected (n = 4) and HCV/HIV-coinfected (n = 5) 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- 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 log₁₀IU/mL and ~ 30%) and coinfected (7.3 log₁₀IU/mL and ~ 40%) participants, the median HCV RNA per infected hepatocyte in monoinfected (2.8IU) was significantly lower than in coinfected (8.2IU) participants (p = .03). Clustering of infected cells was more prominent in monoinfected participants (91% of samples) than in coinfected participants (~48%), p = .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.more » 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-infected cells, but to a less extent the fraction of HCV-infected cells.« less

Authors:

Goyal, Ashish  ^[1];

• Search DOE PAGES for author "Goyal, Ashish"
• Search DOE PAGES for ORCID "0000-0003-1582-3379"

Perelson, Alan S.  ^[2];

• Search DOE PAGES for author "Perelson, Alan S."
• Search DOE PAGES for ORCID "0000-0002-2455-0002"

Kandathil, Abraham J. ^[3]; Quinn, Jeffrey ^[3]; Balagopal, Ashwin ^[3]; Ribeiro, Ruy M.  ^[4]

• Search DOE PAGES for author "Ribeiro, Ruy M."
• Search DOE PAGES for ORCID "0000-0002-3988-8241"

---

+ Show Author Affiliations

1. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States); Fred Hutchinson Cancer Research Center, Seattle, WA (United States)
2. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
3. Johns Hopkins University, Baltimore, MD (United States)
4. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States); University of Lisbon (Portugal)

Publication Date:

Fri Oct 30 00:00:00 EDT 2020

Research Org.:

Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

Sponsoring Org.:

USDOE National Nuclear Security Administration (NNSA)National Institutes of Health (NIH)

OSTI Identifier:

1893668

Report Number(s):

LA-UR-21-20788
Journal ID: ISSN 1352-0504

Grant/Contract Number:  

89233218CNA000001; R01-AI116868; R01-AI028433 24; R01-OD011095; R01-AI078881; R01-DA016078

Resource Type:

Accepted Manuscript

Journal Name:

Journal of Viral Hepatitis

Additional Journal Information:

Journal Volume: 28; Journal Issue: 2; Journal ID: ISSN 1352-0504

Publisher:

Wiley

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; spatial; mathematical model; biopsy; single-cell laser capture microdissection; coinfection