Table 2 The role of let-7 family members in viral infections

HBV

Let-7g

Up

preS2

In vitro

(Hep38.7)

Anti-HBV activity

Decreased level of HBV cccDNA and HBV replication

[115]

HBV

Let-7a

Down

c-myc

CCR7

K-RAS

Human (tissue samples of HCC, n = 20)

/in vitro

(Huh-7)

HBV mRNAs (pre-C/C, pre-S, and S) promoted the progression of HCC by decreasing the expression level of let-7a. mRNAs de-repressed let-7a targets, including c-myc, K-RAS, and CCR7

[116]

HBV

Let-7a

Down

STAT3

In vitro

(HBx-HepG2)

HBX protein enhanced cell proliferation by decreasing the expression level of let-7a

[124]

HBV

Let-7i

Down

CD59

Human (HCC tissues samples)/

in vitro

(HBx-HepG2,

HBx-L-O2)

HBx increased CD59 expression through (probable) downregulation of let-7i levels

[125]

HCV

Let-7c

Up

Bach1

In vitro

(Ava.5/

JFH1-Huh7)

Anti-HCV activity

let‐7c suppressed HCV replication by targeting Bach1

[138]

HCV

Let-7b

Up

SOCS1

IKKα

ATG12

In vitro

(Huh7)

Anti-HCV activity

let-7b inhibited HCV by enhancing JAK/STAT and RIG-I signaling pathways during the early stage of HCV infection

[142]

HCV

Let-7b

Up

IGF2BP1

In vitro

(IFN-α

and IL-28B

treated Huh7, Huh7.5.1)

Anti-HCV activity by targeting IGF2BP1

Let-7 s reduced HCV replication and translation

[137]

HCV

(genotype

1b, 2a)

Let-7g

Up

5′-UTR of HCV genome

In vitro

(PEG-IFN/RBV-treated Ava.5-

Huh7, JFH1-Huh7.5.1)

Anti-HCV activity

Let-7g cooperated with interferon/ribavirin to repress hepatitis C virus replication through p38/AP-1 signaling

[287]

HCV

(genotype 1b)

Let-7b

Up

NS5B

5′UTR

In vitro (Huh-7)

Anti HCV activity

Let-7b suppressed replication and translation of HCV by targeting NS5B and the 5′-UTR region of HCV genome

[135]

HCV

(genotype 1b)

Let-7a

Down

CLDN1

CDH1

Human (tissue samples of chronic HCV)/in vitro

(Huh7.5.1, PHH)

Let-7a was significantly downregulated by HCV

Let-7a and 7b restricted multiple steps of the HCV life cycle, including entry, translation, and RNA replication

[139]

HIV-1

Let-7c

Up

CDKN1A, at the RNA and protein (p21) levels

In vitro

(T lymphocytes,

HeLa-CCR5)

Let-7c was upregulated on the first day after HIV infection and downregulated at later timepoints. Upregulation of has-let-7c levels resulted in enhanced HIV replication

[256]

HIV-1

Let-7i

Down

IL-2 promoter TATA-box region

In vitro

(CD4⁺ T cell)

HIV-1 infection attenuated the expression of let-7i and promoted the activity of IL-2

[250]

HIV-1

Let-7b

Let-7c

Let-7f

Down

IL-10

In vitro (HUT78)

Let-7 decreased IL-10 levels

Downregulation of let-7 miRNAs by HIV infection may result in an increase in IL-10 secretion from CD4⁺ T cells, providing the virus with a survival advantage

[123]

HHV-8

Let-7a

Up

RBPJ

In vitro (293 T)

LANA protein repressed lytic replication of HHV-8 by upregulating let-7a expression and promoting notch intracellular domain (NICD) and decreasing LIN28B and NF-κB

[170]

HHV-8

Let-7a

Let-7d

Let-7e

Let-7i

Down

MAP4K4

Human (tissue samples, n = 4) /in vitro (293 T)

Anti-KSHV activity

Let-7a inhibited replication of KSHV by targeting MAP4K4 signaling pathways

[169]

HPV-16 and HPV-18

Let-7a

Down

STAT3

Human (tissue samples of cervical cancer, n = 53)/in vitro (CaSki, SiHa, HeLa)

E6 increased expression level of STAT3 by downregulation of let-7a

[192]

EBV

Let-7a-5p

Let-7b-5p

Let-7d

Let-7e-5p

Let-7f-5p

Let-7g-5p

Up

BZLF1

Dicer

In vitro (HONE1, CNE2Z)

EBV EBNA1 promoted EBV latency by inducing the expression of let-7

[153]

SARS-CoV-2

Let7-d-3p

Let7-e-3p

Let7-f-3p

Let7g-3p

Let7-i-3p

Up

S

In vitro

Has-let-7 repressed SARS-CoV-2 replication by targeting S gene of virus

[219]

SARS-CoV-2

Let7-b-3p

Let7-c-3p

let7g-3p

Let7-i-3p

Up

M

In vitro

let-7c-5p can target the ORF1ab SARS-CoV-2 to inhibit its replication

[219]

H1N1

Let-7c

Up

M1

In vitro (A549)

Inhibited virus replication

[209]

H7N9

Avian

Let-7e

Down

IL-6

In vitro (THP‑1)

The expression of pro-inflammatory factors IL‑6, IL‑1α, and IL‑1β was promoted through the effect of HA protein on let-7e expression

[320]

RSV

Let-7f

Up

SOCS3

CCND1

ELF4

DYRK2

CCL7

In vitro (A549)

G protein stimulated expression of let-7f, to promote virus replication

[223]

RSV

Let-7f

Down

IFN λ

In vitro

(Calu-3)

G protein led to escape from interferon response by altering expression of let-7f

[227]

DENV-2

Let-7e

Up

SOCS3

In vitro (PBMC)

Enhanced the level of pro-inflammatory cytokines during infection

[321]

DENV-2

Let-7a

Up

NS1

In vitro (Huh-7)

Decreased NS1 RNA and protein expression, repressed DENV virus replication and pathogenesis

[322]

Enterovirus 71

let‑7c‑

5p

Up

MAP4K4

In vitro

(rhabdomyosarcoma)

Hsa-let-7c-5p promoted enterovirus 71 replication by activating the JNK signaling pathway

[323]

Enterovirus 71

Let-7b

Up

CCND1

In vitro (SH-SY5Y)

Increased cell apoptosis

[324]

Enterovirus 71

Let-7a

Up

VP2

5′UTR

In vitro

(SK-N-SH, RD)

Suppressed virus replication and decreased viral load

[325]

Pestivirus

Let-7a

Let-7b

Up

3′-UTR

In vitro

(MDBK)

Promoted virus replication, translation, and RNA stability

[326]

Porcine reproductive and respiratory syndrome virus

Let-7f-5p

Down

MYH9

In vitro

(HEK293FT)

Repressed virus replication

[327]