# Immune Evasion Mechanisms of KSHV Complement and Fc-Receptor Proteins

> **NIH NIH K99** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2023 · $109,860

## Abstract

PROJECT ABSTRACT
Kaposi sarcoma-associated herpesvirus (KSHV) is the causal agent of Kaposi sarcoma, a cancer that appears
as tumors on the skin or mucosal surfaces, and two types of B-cell lymphomas, multicentric Castleman disease
and primary effusion lymphoma. As there are no vaccines or therapeutic treatments to successfully prevent or
eradicate KSHV, in part due to its ability to evade its host’s immune defenses, it remains a significant public
health burden. Although B-cell lymphomas are rare, more than 44,000 new cases of Kaposi sarcoma are
reported globally each year. Thus, there is a critical need to elucidate the mechanisms by which KSHV escapes
the human immune system. Herpesviruses, including KSHV, co-evolved with their hosts over millions of years,
hijacking host regulatory factors to camouflage themselves and evade a wide range of host defense measures.
Notably, like other herpesviruses, KSHV has acquired a complement control protein (KCP) found to modulate
the host complement-mediated immune defense. Unfortunately, studies of KCP in a biologically relevant setting
have been hindered by the absence of a system to produce KCP-null KSHV and test the effects of KCP–
complement interactions on virus-infected cells. To address these deficiencies, we generated recombinant KSHV
(rKSHV) lacking KCP (rKSHVΔKCP) using newly established KSHV bacterial artificial chromosome (BAC)
technology, as well as novel anti-KCP antibodies to characterize the mutant virus. During the mentored (K99)
phase, I will use these resources to characterize the role of KCP in evading complement control and infection.
In addition to KCP, KSHV encodes a glycoprotein, K1, that has acquired immunoglobulin structure domains with
fragment crystallizable receptor (FcR) functions. Similar domains in other herpesviruses have been shown to act
as distractor receptors for host antiviral antibodies that typically bind FcRs present on immune cells; however,
the role of K1 in Fc-mediated immune evasion by KSHV has not been examined. Therefore, toward the end of
the K99 phase, I propose to generate and characterize anti-K1 antibodies and characterize our recently
generated stable rKSHVΔK1 producer cell lines. These resources will be utilized in the independent (R00) phase
to characterize the Fc-type interactions and binding capabilities of K1. I will also study the mechanism by which
K1 interferes with host FcR activation using a novel reporter assay. Finally, I will evaluate the efficacy of anti-K1
antibodies in blocking Fc-mediated immune evasion. Thus, the studies proposed herein will provide a better
understanding of the role of KCP and K1 in host immune evasion. This work will greatly enhance the development
of effective strategies to prevent and control KSHV infection and pathogenesis. Furthermore, the research and
training proposed for the K99 phase will provide experience and knowledge in viral genomics/proteomics,
immunobiology, and viral oncology, as well as a significant...

## Key facts

- **NIH application ID:** 10679000
- **Project number:** 5K99AI159139-02
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** MURALI BAGALUR MUNIRAJU
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $109,860
- **Award type:** 5
- **Project period:** 2022-09-12 → 2024-09-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10679000

## Citation

> US National Institutes of Health, RePORTER application 10679000, Immune Evasion Mechanisms of KSHV Complement and Fc-Receptor Proteins (5K99AI159139-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10679000. Licensed CC0.

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